Phase 1b/2 study of Carfilzomib in relapsed or refractory ALL children
Research type
Research Study
Full title
Phase 1b/2 Study of Carfilzomib in Combination with Dexamethasone, Mitoxantrone, PEG-asparaginase, and Vincristine (UK R3 Induction Backbone) in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia
IRAS ID
163213
Contact name
Donna Lancaster
Contact email
Sponsor organisation
Amgen Limited
Eudract number
2014-001633-84
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Summary of Research
This research is planned for the participants whose acute lymphoblastic leukaemia (ALL- a cancer of white blood cells) has relapsed or been refractory to treatment. Relapse means the leukaemia has come back after treatment. Refractory means that the leukaemia did not go away during treatment.
Carfilzomib (KyprolisTM) is a drug approved by the Food and Drug Administration for the treatment of some adults with relapsed multiple myeloma, which is a type of blood cancer. It is not approved to treat ALL, it has not been given in combination with the other drugs used in this study. Carfilzomib is a type of drug called a proteasome inhibitor and works by preventing breakdown of proteins in cells, causing the cells to die. Cancer cells are more sensitive to these effects than normal cells. This study is being done to find out if carfilzomib can be safely given before and during treatment with standard chemotherapy drugs.
The study has two parts. There will be a phase 1b part and phase 2 part, in a phase 1b study the drugs are tested to evaluate the dosage that can be safely given. Drugs are given at different dosages until the highest dose without unacceptable side effects is found. In a Phase 2 study, the dose that is found to be safe in the Phase 1 study is used and its effectiveness against the cancer is evaluated. During the Phase 1b portion of the study only, the Induction Cycle will be preceded by a 1-week carfilzomib single-agent Lead-in Window. Participants in both the Phase 1b and Phase 2 portions of the study will receive a 4-week cycle of induction chemotherapy and have the option to receive a 4-week cycle of consolidation chemotherapy, if SD or better response is achieved at the end of the Induction Cycle.
Summary of Results
. Study Name
Title of the Study: Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Brief Title: Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
Protocol Number: 20140106
EU Trial Number: 2014-001633-84
Other Identifiers: NCT02303821
Date of This Summary: 18 November 2024What does this summary cover?
This summary shows the main results from one clinical study. Some of the results were compared with the results from a different study. Other studies may find different results. Researchers and health authorities look at the results of many studies to decide which medicines work best and are safest for patients.
Amgen has committed to make research results available to the public. This summary has been provided as part of that commitment and should not be used for any other purpose. It should not be considered to make a claim for any product or to guide treatment decisions.2. Who Sponsored This Study?
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 USA
Phone (United States): +1 805-447-1000
Phone (United Kingdom): +44 1223 436441
Amgen Inc. is the sponsor of the study who made carfilzomib (Kyprolis), the medicine tested in the study. Amgen would like to thank the children who participated in this study, and their families, and feels it is important to share the results of this study.3. General Information About the Clinical Study
Where and when was the study done?
The study was split into 2 parts called phase 1b and phase 2. Each participant was either in phase 1b or phase 2. Results for each phase are presented separately throughout the document.
Phase 1b
• This study took place in Australia, Austria, Canada, Denmark, France, Israel, Italy, Spain, the United Kingdom, and the United States.
• The study began in February 2015 and ended in October 2020.
• The study was completed as planned.Phase 2
• This study took place in Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Denmark, France, Greece, Hong Kong, Italy, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russia, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey, and the United States.
• The study began in September 2021 and ended in June 2024.
• The study was completed as planned.
Why was the study done?
Acute lymphoblastic leukemia (ALL) is a type of cancer of the white blood cells. ALL happens when the bone marrow produces too many abnormal B cells (called B-cell ALL) or T cells (called T-cell ALL). Patients can be treated for ALL. However, ALL might come back after treatment or might not respond to treatment (called relapsed or refractory ALL). Patients with relapsed ALL need further treatment. Researchers are looking for new ways to treat relapsed ALL.
Carfilzomib is a type of treatment known as a proteasome inhibitor. Carfilzomib may prevent the breakdown of abnormal proteins in cells, causing these cells to die. Cancer cells are more sensitive to these effects than normal cells. Carfilzomib is usually used to treat adult patients with another type of cancer, called multiple myeloma. This study was the first time carfilzomib was given to patients with ALL and to children.
Phase 1b
• This was a phase 1b study conducted as part of the early process to test how a medicine approved for one disease in adults may work in another type of cancer in children. Researchers looked at how this medicine works in the body when given together with medicines used to treat ALL, a combination of medicines that has not been studied previously.
• Participants were given carfilzomib in combination with induction chemotherapy.
• Researchers initially used a combination of chemotherapy treatments called R3 (dexamethasone, mitoxantrone, polyethylene glycol [PEG]-asparaginase, and vincristine) as the induction chemotherapy in this study. However, due to side effects (unwanted medical problems that may happen when you take a medicine), researchers switched to giving another combination of chemotherapy treatments called VXLD (vincristine, dexamethasone, PEG-asparaginase, and daunorubicin) as induction chemotherapy.
• The first cycle of treatment was called the induction cycle and lasted 28 days.
• The main purpose of the phase 1b study was to find out:
o what side effects occur and how someone feels during treatment with carfilzomib alone and in combination with induction chemotherapy, for the treatment of children with relapsed or refractory ALL
o the highest dose of carfilzomib that participants could take in combination with induction chemotherapy without having too many side effects and to recommend the phase 2 dose of carfilzomib in combination with induction chemotherapy
Phase 2
• This was a phase 2 study, the second part of the development of medicines for humans. Researchers wanted to learn if this new study medicine could help children with ALL.
• Participants were given carfilzomib in combination with induction chemotherapy, which was VXLD chemotherapy in the phase 2 study.
• The first cycle of treatment was called the induction cycle and lasted 28 days.
• The main purpose of the phase 2 study was to find out how many participants had complete remission (all signs and symptoms of ALL disappeared) after treatment with carfilzomib in combination with induction chemotherapy (VXLD chemotherapy). This was compared with the results for a similar group of children with ALL who were part of a different study and were given typical medicines used to treat cancer, called the external control group.4. Who Was Included in This Study?
Who took part in the study?
Phase 1b
This phase of the study included 35 participants with ALL. 11 participants (31%, or about 3 out of 10) were girls and 24 participants (69%, or about 7 out of 10) were boys. They ranged in age from 1 to 19 years. 3 participants (9%, or about 1 out of 10) were younger than 2 years old, 19 participants (54%, or about 5 out of 10) were between 2 and 11 years old, 11 participants (31%, or about 3 out of 10) were between 12 and 17 years old, and 2 participants (6%, or about 1 out of 10) were 18 years or older.
This phase of the study took place at 25 study centers across 9 countries. The numbers of participants in each country are listed below:
• Austria: 1
• Italy: 2
• Australia: 8
• Denmark: 2
• Spain: 2
• Israel: 1
• France: 2
• United Kingdom: 2
• United States: 15
Participants were examined by a study doctor and chosen to be in the study if they:
• were diagnosed with relapsed or refractory ALL
• had been given at least 1 other treatment for ALL before
• were at least 1 year old and younger than 21 years old
Phase 2
This phase of the study included 105 participants with ALL. 1 additional participant left the study before receiving any study medicine and is not included in the results. 61 out of 105 participants had B-cell ALL and 44 out of 105 participants had T-cell ALL, all of whom were given carfilzomib in combination with VXLD chemotherapy. Out of the 61 participants with B-cell ALL, 19 participants (31%, or about 3 out of 10) were girls and 42 participants (69%, or about 7 out of 10) were boys. They ranged in age from 1 year to 19 years. 57 participants (93%, or about 9 out of 10) were 17 years old or younger and 4 participants (7%, or about 1 out of 10) were older than 17 years.
Out of the 44 participants with T-cell ALL, 5 participants (11%, or about 1 out of 10) were girls and 39 participants (89%, or about 9 out of 10) were boys. They ranged in age from 3 years to 19 years. 41 participants (93%, or about 9 out of 10) were 17 years old or younger and 3 participants (7%, or about 1 out of 10) were older than 17 years.
This phase of the study took place at 106 study centers across 22 countries. The numbers of participants in each country are listed below:
• Austria: 2
• Australia: 4
• Singapore: 1
• Bulgaria: 1
• Brazil: 24
• South Africa: 1
• Greece: 4
• Chile: 1
• South Korea: 6
• Italy: 9
• Colombia: 1
• Taiwan: 5
• Portugal: 2
• Hong Kong: 1
• Turkey: 14
• Romania: 7
• Mexico: 3
• United States: 3
• Spain: 11
• Russia: 3
• Argentina: 2
• Saudi Arabia: 1
Participants were examined by a study doctor and chosen to be in the study if they:
• were diagnosed with relapsed or refractory ALL
• had responded to previous cancer treatment
• were at least 1 month old and younger than 21 years old (and were diagnosed with ALL before they were 18 years old)
The external control group included 140 similar children with ALL; 80 of the 140 children had B-cell ALL and 60 of the 140 children had T-cell ALL.
Out of the 80 children with B-cell ALL in the external control group, 32 children (40%, or about 4 out of 10) were girls and 48 children (60%, or about 6 out of 10) were boys. They ranged in age from less than 1 year to 19 years. 72 children (90%, or about 9 out of 10) were 17 years old or younger and 8 children (10%, or about 1 out of 10) were older than 17 years.
Out of the 60 children with T-cell ALL in the external control group, 22 children (37%, or about 4 out of 10) were girls and 38 participants (63%, or about 6 out of 10) were boys. They ranged in age from less than 1 year to 18 years. 55 children (92%, or about 9 out of 10) were 17 years old or younger and 5 children (8%, or about 1 out of 10) were older than 17 years.5. Which Medicines Were Studied?
Phase 1b
All 35 participants in the phase 1b study were given carfilzomib by infusion and the study medicine was given over a period of about 30 minutes. The study medicine was given through a central line or using a needle placed into a vein in the arm.
This was a dose escalation phase of the study, meaning the dose of carfilzomib given during the 28-day induction cycle was increased for each new group of participants. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of the 28-day induction cycle.
The first group of participants in the study were also given carfilzomib alone on days 1 and 2 of a 7-day period (called a lead-in window) before starting the 28-day induction cycle. The participants were assessed after completing the lead-in window. They were then given the lowest dose of carfilzomib (called Dose 1) in combination with R3 chemotherapy during the 28-day induction cycle.
The second group of participants were also given carfilzomib alone on days 1 and 2 of a lead-in window before starting the 28-day induction cycle. During the induction cycle, they received a higher dose of carfilzomib (called Dose 2) in combination with R3 chemotherapy. 1 participant in the Dose 2 group did not receive any study medicine after the lead-in window and so did not receive carfilzomib in combination with R3 chemotherapy.
Due to side effects, researchers switched to giving carfilzomib in combination with VXLD chemotherapy instead of R3 chemotherapy. A 7-day lead-in window was not used for the remainder of the study.
The third group of participants were given Dose 3 of carfilzomib in combination with VXLD chemotherapy during the 28-day induction cycle. Each new group was given a higher dose (Doses 4 to 6) until the dose review committee agreed on the recommended phase 2 dose.
In total, 11 out of the 35 participants were in the R3 chemotherapy group and 24 out of the 35 participants were in the VXLD chemotherapy group. The number of participants in each group is listed below:
• Carfilzomib Dose 1 with R3 chemotherapy: 5 participants
• Carfilzomib Dose 2 with R3 chemotherapy: 6 participants
• Carfilzomib Dose 3 with VXLD chemotherapy: 3 participants
• Carfilzomib Dose 4 with VXLD chemotherapy: 7 participants
• Carfilzomib Dose 5 with VXLD chemotherapy: 4 participants
• Carfilzomib Dose 6 with VXLD chemotherapy: 10 participants
Participants were assessed after the induction cycle and could receive an optional second cycle of treatment, called a consolidation cycle, if their ALL was stable (neither increasing or decreasing in extent or severity) or had improved. The consolidation cycle lasted 28 days and included carfilzomib in combination with chemotherapy (6-mercaptopurine, cyclophosphamide, cytarabine, PEG-asparaginase, and vincristine). Carfilzomib was given by a 30-minute infusion on days 1, 2, 8, 9, 15, and 16. In total, 15 out of the 35 participants were given a consolidation cycle. The number of participants from each group who were given a consolidation cycle is listed below:
• Carfilzomib Dose 1 with R3 chemotherapy: 2 participants
• Carfilzomib Dose 2 with R3 chemotherapy: 1 participant
• Carfilzomib Dose 3 with VXLD chemotherapy: 1 participant
• Carfilzomib Dose 4 with VXLD chemotherapy: 5 participants
• Carfilzomib Dose 5 with VXLD chemotherapy: 3 participants
• Carfilzomib Dose 6 with VXLD chemotherapy: 3 participants
In addition to the treatments listed above, participants with leukemia in their spinal fluid were also given a combination of cytarabine, hydrocortisone, and methotrexate into the spinal canal (intrathecal triple therapy) during the study. Participants without leukemia in their spinal fluid were given methotrexate into the spinal canal.Phase 2
All 105 participants were given carfilzomib in combination with induction chemotherapy (VXLD chemotherapy). This induction cycle lasted for 28 days. The recommended phase 2 dose of carfilzomib was given by infusion and the study medicine was given over a period of about 30 minutes. The study medicine was given through a central line or using a needle placed into a vein in the arm on days 1, 2, 8, 9, 15, and 16.
Participants were assessed after the induction cycle and could receive an optional second cycle of treatment, called a consolidation cycle, if their ALL had not worsened. The consolidation cycle lasted 28 days and included carfilzomib in combination with chemotherapy (6-mercaptopurine, cyclophosphamide, cytarabine, PEG-asparaginase, and vincristine). Carfilzomib was given by a 30-minute infusion on days 1, 2, 8, 9, 15, and 16. In total, 45 out of the 105 participants were given a consolidation cycle:
• 25 out of 61 participants with B-cell ALL
• 20 out of 44 participants with diagnosis of T-cell ALL
In addition to the treatments listed above, participants with leukemia in their spinal fluid were also given a combination of cytarabine, hydrocortisone, and methotrexate into the spinal canal (intrathecal triple therapy) during the study. Participants without leukemia in their spinal fluid were given methotrexate into the spinal canal.6. What Were the Side Effects?
What is a side effect?
All medicines can cause side effects, or unwanted medical problems that may happen when you take a medicine. In this study, doctors reported all the medical problems participants had. Doctors believed some of the problems could have been caused by the study medicine. These possible side effects are listed below.What side effects were seen?
Phase 1b
The table below shows how many participants in the R3 chemotherapy group had side effects during the phase 1b study. Some participants may have had a side effect in more than 1 cycle of treatment but are counted only once in the total column.Side Effects in the R3 Chemotherapy Group During the Phase 1b Study
How many participants had serious side effects?
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 2 participants (33%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 2 participants (100%)
Consolidation Cycle Dose 2 (1 participant) 1 participant (100%)
Total All Cycles/Doses (11 participants) 7 participants (64%)How many participants had non-serious side effects?
Lead-in Window Dose 1 (5 participants) 5 participants (100%)
Lead-in Window Dose 2 (6 participants) 4 participants (67%)
Induction Cycle Dose 1 (5 participants) 4 participants (80%)
Induction Cycle Dose 2 (5 participants) 4 participants (80%)
Consolidation Cycle Dose 1 (2 participants) 1 participant (50%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 9 participants (82%)
How many participants died from side effects?
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 0 participants (0%)
Induction Cycle Dose 1 (5 participants) 0 participants (0%)
Induction Cycle Dose 2 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 0 participants (0%)How many participants stopped taking the study medicine because of side effects?
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 0 participants (0%)
Induction Cycle Dose 1 (5 participants) 0 participants (0%)
Induction Cycle Dose 2 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 1 participant (9%)The table below shows how many participants in the VXLD chemotherapy group had side effects during the phase 1b study. Some participants may have had a side effect in more than 1 cycle of treatment but are counted only once in the total column.
Side Effects in the VXLD Chemotherapy Group During the Phase 1b Study
How many participants had serious side effects?
Induction Cycle Dose 3 (3 participants) 2 participants (67%)
Induction Cycle Dose 4 (7 participants) 2 participants (29%)
Induction Cycle Dose 5 (4 participants) 3 participants (75%)
Induction Cycle Dose 6 (10 participants) 4 participants (40%)
Consolidation Cycle Dose 3 (1 participant) 1 participant (100%)
Consolidation Cycle Dose 4 (5 participants) 4 participants (80%)
Consolidation Cycle Dose 5 (3 participants) 3 participants (100%)
Consolidation Cycle Dose 6 (3 participants) 3 participants (100%)
Total All Cycles/Doses (24 participants) 18 participants (75%)How many participants had nonserious side effects?
Induction Cycle Dose 3 (3 participants) 2 participants (67%)
Induction Cycle Dose 4 (7 participants) 6 participants (86%)
Induction Cycle Dose 5 (4 participants) 4 participants (100%)
Induction Cycle Dose 6 (10 participants) 7 participants (70%)
Consolidation Cycle Dose 3 (1 participant) 1 participant (100%)
Consolidation Cycle Dose 4 (5 participants) 5 participants (100%)
Consolidation Cycle Dose 5 (3 participants) 2 participants (67%)
Consolidation Cycle Dose 6 (3 participants) 2 participants (67%)
Total All Cycles/Doses (24 participants) 20 participants (83%)How many participants died from side effects?
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 0 participants (0%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 1 participant (4%)How many participants stopped taking the study medicine because of side effects?
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 0 participants (0%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 3 participants (30%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)If a participant had to stay in the hospital or died because of a side effect, the doctor reported that the side effect was serious. One participant in the phase 1b study died because of a side effect of lung infection.
The table below shows the serious side effects that occurred in at least 2 participants in the R3 chemotherapy group. Some participants may have had the same side effect in more than 1 cycle of treatment but are counted only once in the total column.Serious Side Effects in the R3 Chemotherapy Group During the Phase 1b Study
Serious side effect:
Fever with low white blood cell count
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 1 participant (17%)
Induction Cycle Dose 1 (5 participants) 1 participant (20%)
Induction Cycle Dose 2 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 1 (2 participants) 2 participants (100%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)Infection in the blood
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 1 participant (17%)
Induction Cycle Dose 1 (5 participants) 1 participant (20%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 3 participants (27%)The table below shows the serious side effects that occurred in at least 2 participants in the VXLD chemotherapy group. Some participants may have had the same side effect in more than 1 cycle of treatment but are counted only once in the total column.
Serious Side Effects in the VXLD Chemotherapy Group During the Phase 1b Study
Serious side effect:
Fever with low white blood cell count
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 0 participants (0%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 1 participant (100%)
Consolidation Cycle Dose 4 (5 participants) 3 participants (60%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 6 participants (25%)Brain swelling with usually temporary effects such as headache, changes in vision, reduced consciousness, and seizures
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 2 participants (29%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 3 participants (13%)Bacteria on the plastic tube in the arm (catheter) 0
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 0 participants (0%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 2 participants (8%)Allergic reaction to a drug
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 0 participants (0%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 2 participants (67%)
Total All Cycles/Doses (24 participants) 2 participants (8%)Short-lived or sudden inflammation of the pancreas, the organ that releases insulin to help control blood sugar and enzymes that help digest food
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 2 participants (8%)The table below shows the non-serious side effects that occurred in at least 4 participants in the R3 chemotherapy group. Some participants may have had the same side effect in more than 1 cycle of treatment but are counted only once in the total column.
Non-serious Side Effects in the R3 Chemotherapy Group During the Phase 1b Study
Non-serious side effect
Low red blood cell count
Lead-in Window Dose 1 (5 participants) 3 participants (60%)
Lead-in Window Dose 2 (6 participants) 2 participants (33%)
Induction Cycle Dose 1 (5 participants) 4 participants (80%)
Induction Cycle Dose 2 (5 participants) 3 participants (60%)
Consolidation Cycle Dose 1 (2 participants) 1 participant (50%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 7 participants (64%)
A blood test that shows an increase in a liver enzyme called alanine aminotransferase
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 1 participant (17%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 1 participant (50%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)High blood sugar
Lead-in Window Dose 1 (5 participants) 0 participants (0%)
Lead-in Window Dose 2 (6 participants) 0 participants (0%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)Low blood albumin (a protein that circulates in the blood)
Lead-in Window Dose 1 (5 participants) 1 participant (20%)
Lead-in Window Dose 2 (6 participants) 0 participants (0%)
Induction Cycle Dose 1 (5 participants) 3 participants (60%)
Induction Cycle Dose 2 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)Low blood calcium
Lead-in Window Dose 1 (5 participants) 1 participant (20%)
Lead-in Window Dose 2 (6 participants) 2 participants (33%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)Low blood magnesium
Lead-in Window Dose 1 (5 participants) 1 participant (20%)
Lead-in Window Dose 2 (6 participants) 1 participants (17%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 1 participant (50%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)Low blood phosphates
Lead-in Window Dose 1 (5 participants) 1 participant (20%)
Lead-in Window Dose 2 (6 participants) 1 participant (17%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 0 participants (0%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)Low platelet count (part of the blood that helps clotting)
Lead-in Window Dose 1 (5 participants) 1 participant (20%)
Lead-in Window Dose 2 (6 participants) 1 participant (17%)
Induction Cycle Dose 1 (5 participants) 2 participants (40%)
Induction Cycle Dose 2 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 1 (2 participants) 1 participants (50%)
Consolidation Cycle Dose 2 (1 participant) 0 participants (0%)
Total All Cycles/Doses (11 participants) 4 participants (36%)The table below shows the non-serious side effects that occurred in at least 4 participants in the VXLD chemotherapy group. Some participants may have had the same side effect in more than 1 cycle of treatment but are counted only once in the total column.
Non-serious Side Effects in the VXLD Chemotherapy Group During the Phase 1b Study
Non-serious side effect
High blood pressure
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 3 participants (43%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 6 participants (60%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 3 participants (60%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 14 participants (58%)Low platelet count (part of the blood that helps clotting)
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 2 participants (29%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 4 participants (40%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 3 participants (60%)
Consolidation Cycle Dose 5 (3 participants) 2 participants (67%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 10 participants (42%)Low red blood cell count
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 3 participants (43%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 2 participants (20%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 4 participants (80%)
Consolidation Cycle Dose 5 (3 participants) 2 participants (67%)
Consolidation Cycle Dose 6 (3 participants) 1 participant (33%)
Total All Cycles/Doses (24 participants) 9 participants (38%)A blood test that shows an increase in a liver enzyme called alanine aminotransferase
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 2 participants (29%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 3 participants (60%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 1 participant (33%)
Total All Cycles/Doses (24 participants) 7 participants (29%)Queasy/feeling like you need to throw up
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 3 participants (43%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 4 participants (80%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 7 participants (29%)Tiredness
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 2 participant (50%)
Induction Cycle Dose 6 (10 participants) 2 participants (20%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 6 participants (25%)Stomach pain
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 5 participants (21%)Fever
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 1 participant (100%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 5 participants (21%)Low blood potassium
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 2 participant (20%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 5 participants (21%)A blood test that shows an increase in a liver enzyme called aspartate aminotransferase
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 3 participants (60%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Constipation
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Loose stools
Induction Cycle Dose 3 (3 participants) 0 participants (0%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 1 participant (10%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 2 participant (40%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Low blood albumin (a protein that circulates in the blood)
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 2 participant (29%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 2 participant (40%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Low blood sodium
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 2 participants (20%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Low blood phosphates
Induction Cycle Dose 3 (3 participants) 0 participant (0%)
Induction Cycle Dose 4 (7 participants) 1 participant (14%)
Induction Cycle Dose 5 (4 participants) 1 participant (25%)
Induction Cycle Dose 6 (10 participants) 2 participants (20%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 0 participants (0%)
Consolidation Cycle Dose 5 (3 participants) 0 participants (0%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Low white blood cell count (neutrophils)
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 2 participants (29%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 1 participant (20%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Low white blood cell count
Induction Cycle Dose 3 (3 participants) 1 participant (33%)
Induction Cycle Dose 4 (7 participants) 2 participants (29%)
Induction Cycle Dose 5 (4 participants) 0 participants (0%)
Induction Cycle Dose 6 (10 participants) 0 participants (0%)
Consolidation Cycle Dose 3 (1 participant) 0 participants (0%)
Consolidation Cycle Dose 4 (5 participants) 2 participants (40%)
Consolidation Cycle Dose 5 (3 participants) 1 participant (33%)
Consolidation Cycle Dose 6 (3 participants) 0 participants (0%)
Total All Cycles/Doses (24 participants) 4 participants (17%)Phase 2
The table below shows how many participants had side effects during the phase 2 study. Some participants may have had a side effect in more than 1 cycle of treatment but are counted only once in the total column.Side Effects During the Phase 2 Study
How many participants had serious side effects?
Induction Cycle B-cell ALL (61 participants) 18 participants (30%)
Induction Cycle T-cell ALL (44 participants) 18 participants (41%)
Consolidation Cycle B-cell ALL (25 participants) 9 participants (36%)
Consolidation Cycle T-cell ALL (20 participants) 10 participants (50%)
Total All Cycles (105 participants) 49 participants (47%)How many participants had non-serious side effects?
Induction Cycle B-cell ALL (61 participants) 43 participants (70%)
Induction Cycle T-cell ALL (44 participants) 35 participants (80%)
Consolidation Cycle B-cell ALL (25 participants) 20 participants (80%)
Consolidation Cycle T-cell ALL (20 participants) 19 participants (95%)
Total All Cycles (105 participants) 82 participants (78%)How many participants died from side effects?
Induction Cycle B-cell ALL (61 participants) 4 participants (7%)
Induction Cycle T-cell ALL (44 participants) 0 participants (0%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 6 participants (6%)How many participants stopped taking the study medicine because of side effects?
Induction Cycle B-cell ALL (61 participants) 5 participants (8%)
Induction Cycle T-cell ALL (44 participants) 5 participants (11%)
Consolidation Cycle B-cell ALL (25 participants) 5 participants (20%)
Consolidation Cycle T-cell ALL (20 participants) 5 participant (25%)
Total All Cycles (105 participants) 20 participants (19%)If a participant had to stay in the hospital or died because of a side effect, the doctor reported that the side effect was serious. 6 participants in the phase 2 study died because of side effects. These included an infection in the blood caused by E. coli bacteria, infection in the blood with low white blood cell count, fungal lung infection, bleeding in the lungs, blockage of the blood vessels that carry oxygen-rich blood from the lungs to the heart, and symptoms of infection in the blood.
The table below shows the serious side effects that occurred in at least 3 participants in the phase 2 study. Some participants may have had the same side effect in more than 1 cycle of treatment but are counted only once in the total columnSerious Side Effects During the Phase 2 Study
Serious side effect
Fever with low white blood cell count
Induction Cycle B-cell ALL (61 participants) 3 participants (5%)
Induction Cycle T-cell ALL (44 participants) 2 participants (5%)
Consolidation Cycle B-cell ALL (25 participants) 3 participants (12%)
Consolidation Cycle T-cell ALL (20 participants) 2 participants (10%)
Total All Cycles (105 participants) 9 participants (9%)Brain swelling with usually temporary effects such as headache, changes in vision, reduced consciousness, and seizures
Induction Cycle B-cell ALL (61 participants) 1 participant (2%)
Induction Cycle T-cell ALL (44 participants) 4 participants (9%)
Consolidation Cycle B-cell ALL (25 participants) 0 participants (0%)
Consolidation Cycle T-cell ALL (20 participants) 0 participants (0%)
Total All Cycles (105 participants) 5 participants (5%)Low platelet count (part of the blood that helps clotting)
Induction Cycle B-cell ALL (61 participants) 0 participants (0%)
Induction Cycle T-cell ALL (44 participants) 3 participants (7%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 2 participants (10%)
Total All Cycles (105 participants) 5 participants (5%)A dangerous drop in blood pressure caused by severe infection
Induction Cycle B-cell ALL (61 participants) 2 participants (3%)
Induction Cycle T-cell ALL (44 participants) 0 participants (0%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 4 participants (4%)A condition that can occur after treatment of a fast-growing cancer. As tumor cells die, they break apart and release their contents into the blood. This causes a change in certain chemicals in the blood, which may cause damage to organs, including the kidneys, heart, and liver
Induction Cycle B-cell ALL (61 participants) 1 participant (2%)
Induction Cycle T-cell ALL (44 participants) 1 participant (2%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 4 participants (4%)Infection in the blood caused by a bacteria called E. coli
Induction Cycle B-cell ALL (61 participants) 1 participant (2%)
Induction Cycle T-cell ALL (44 participants) 1 participant (2%)
Consolidation Cycle B-cell ALL (25 participants) 0 participants (0%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 3 participants (3%)Fungal lung infection
Induction Cycle B-cell ALL (61 participants) 2 participants (3%)
Induction Cycle T-cell ALL (44 participants) 1 participant (2%)
Consolidation Cycle B-cell ALL (25 participants) 0 participants (0%)
Consolidation Cycle T-cell ALL (20 participants) 0 participants (0%)
Total All Cycles (105 participants) 3 participants (3%)The table below shows the non-serious side effects that occurred in at least 10 participants in the phase 2 study. Some participants may have had the same side effect in more than 1 cycle of treatment but are counted only once in the total column.
Non-serious Side Effects During the Phase 2 Study
Non-serious side effect
Low red blood cell count
Induction Cycle B-cell ALL (61 participants) 14 participants (23%)
Induction Cycle T-cell ALL (44 participants) 17 participants (39%)
Consolidation Cycle B-cell ALL (25 participants) 6 participants (24%)
Consolidation Cycle T-cell ALL (20 participants) 5 participants (25%)
Total All Cycles (105 participants) 32 participants (30%)Low white blood cell count (neutropenia)
Induction Cycle B-cell ALL (61 participants) 14 participants (23%)
Induction Cycle T-cell ALL (44 participants) 11 participants (25%)
Consolidation Cycle B-cell ALL (25 participants) 4 participants (16%)
Consolidation Cycle T-cell ALL (20 participants) 9 participants (45%)
Total All Cycles (105 participants) 30 participants (29%)Low platelet count (part of the blood that helps clotting)
Induction Cycle B-cell ALL (61 participants) 9 participants (15%)
Induction Cycle T-cell ALL (44 participants) 13 participants (30%)
Consolidation Cycle B-cell ALL (25 participants) 6 participants (24%)
Consolidation Cycle T-cell ALL (20 participants) 4 participants (20%)
Total All Cycles (105 participants) 28 participants (27%)High blood pressure
Induction Cycle B-cell ALL (61 participants) 13 participants (21%)
Induction Cycle T-cell ALL (44 participants) 11 participants (21%)
Consolidation Cycle B-cell ALL (25 participants) 2 participants (8%)
Consolidation Cycle T-cell ALL (20 participants) 1 participants (5%)
Total All Cycles (105 participants) 25 participants (24%)Fever
Induction Cycle B-cell ALL (61 participants) 8 participants (13%)
Induction Cycle T-cell ALL (44 participants) 8 participants (18%)
Consolidation Cycle B-cell ALL (25 participants) 5 participants (20%)
Consolidation Cycle T-cell ALL (20 participants) 7 participants (35%)
Total All Cycles (105 participants) 25 participants (24%)A blood test that shows an increase in a liver enzyme called alanine aminotransferase
Induction Cycle B-cell ALL (61 participants) 9 participants (15%)
Induction Cycle T-cell ALL (44 participants) 8 participants (18%)
Consolidation Cycle B-cell ALL (25 participants) 4 participants (16%)
Consolidation Cycle T-cell ALL (20 participants) 6 participants (30%)
Total All Cycles (105 participants) 23 participants (22%)Fever with low white blood cell count
Induction Cycle B-cell ALL (61 participants) 6 participants (10%)
Induction Cycle T-cell ALL (44 participants) 6 participants (14%)
Consolidation Cycle B-cell ALL (25 participants) 3 participants (12%)
Consolidation Cycle T-cell ALL (20 participants) 6 participants (30%)
Total All Cycles (105 participants) 20 participants (19%)A blood test that shows an increase in a liver enzyme called aspartate aminotransferase
Induction Cycle B-cell ALL (61 participants) 7 participants (11%)
Induction Cycle T-cell ALL (44 participants) 5 participants (11%)
Consolidation Cycle B-cell ALL (25 participants) 5 participants (20%)
Consolidation Cycle T-cell ALL (20 participants) 4 participants (20%)
Total All Cycles (105 participants) 18 participants (17%)Low white blood cell count (leukopenia)
Induction Cycle B-cell ALL (61 participants) 5 participants (8%)
Induction Cycle T-cell ALL (44 participants) 9 participants (20%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 2 participants (10%)
Total All Cycles (105 participants) 15 participants (14%)Low blood potassium
Induction Cycle B-cell ALL (61 participants) 5 participants (8%)
Induction Cycle T-cell ALL (44 participants) 4 participants (9%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 2 participants (10%)
Total All Cycles (105 participants) 12 participants (11%)Low white blood cell count
Induction Cycle B-cell ALL (61 participants) 8 participants (13%)
Induction Cycle T-cell ALL (44 participants) 4 participants (9%)
Consolidation Cycle B-cell ALL (25 participants) 4 participants (16%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 12 participants (11%)Low blood albumin (a protein that circulates in the blood)
Induction Cycle B-cell ALL (61 participants) 8 participants (13%)
Induction Cycle T-cell ALL (44 participants) 2 participants (5%)
Consolidation Cycle B-cell ALL (25 participants) 2 participants (8%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 11 participants (10%)Low white blood cell count (neutrophils)
Induction Cycle B-cell ALL (61 participants) 6 participants (10%)
Induction Cycle T-cell ALL (44 participants) 4 participants (9%)
Consolidation Cycle B-cell ALL (25 participants) 1 participant (4%)
Consolidation Cycle T-cell ALL (20 participants) 1 participant (5%)
Total All Cycles (105 participants) 10 participants (10%)This section only shows the most often reported side effects considered by the study doctor as related to study medicine. No single clinical study can give a complete picture of the benefits and risks of a medicine. Information about other side effects may be available at the websites listed at the end of this summary.
7. What Were the Overall Results of the Study?
Phase 1b
• The chemotherapy was changed from R3 chemotherapy to VXLD chemotherapy due to side effects seen in participants treated with carfilzomib in combination with R3 chemotherapy.
• The side effects reported for carfilzomib in combination with VXLD were similar to the known side effects of these treatments and were manageable. No new safety findings were observed.
Phase 2
How many participants had complete remission after treatment with carfilzomib in combination with induction chemotherapy?
• Participants with B-cell ALL:
o 9 out of 61 participants with B-cell ALL (15%, or about 15 out of 100) had complete remission after treatment with carfilzomib in combination with VXLD chemotherapy.
o This was compared with 8% (or about 8 out of 100) similar children with B-cell ALL who were part of a different study and were given typical medicines used to treat cancer.
• Participants with T-cell ALL:
o 6 out of 44 participants with T-cell ALL (14%, or about 14 out of 100) had complete remission after treatment with carfilzomib in combination with VXLD chemotherapy.
o This was compared with 9 % (or about 9 out of 100) similar children with T-cell ALL who were part of a different study and were given typical medicines used to treat cancer.
• These results did not statistically show that carfilzomib in combination with VXLD chemotherapy was better than VXLD chemotherapy alone. The differences seen could have been due to chance.
• The side effects reported for carfilzomib in combination with VXLD were similar to the known side effects of these treatments and were manageable. No new safety findings were observed.
• More results may be available at the websites listed at the end of this summary.8. How Has This Study Helped Participants and Researchers?
What else is important to know about these results?
These results are only for this clinical study, which looked at a sample of 35 children with ALL in the phase 1b study and 105 children with ALL in the phase 2 study. Not all participants in the phase 1b and phase 2 study had the same results. The results for any single participant could have been better or worse than the results for their group. Other studies may find different results. These results do not explain how a study medicine may work in a single person. Many studies are needed to show the benefits and risks of a medicine that is still being tested. This research may help future participants and families by helping doctors understand more about the study medicine being studied.9. Are There Plans for Further Studies?
Amgen does not currently plan to conduct any further studies with carfilzomib in this disease.10. Where Can I Find More Information About This Study?
To find out more about this study, check these websites:
• https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Clondoncentral.rec%40hra.nhs.uk%7C5143841a9ecd4e6d025a08dd51c5ce81%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638756632187991716%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=N29Wq%2BVQN8Z4hojcdNWUAM%2BCgGcgYW20rgHsGXHGfAc%3D&reserved=0. Use the study identifier 2014-001633-84.
• https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Clondoncentral.rec%40hra.nhs.uk%7C5143841a9ecd4e6d025a08dd51c5ce81%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638756632188028427%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=xkcEGu%2BCcUZyO5uSwC0Or%2BqjtYkvE%2BUDoE%2B5hkqtphc%3D&reserved=0. Use the study identifier NCT02303821
• Burke MJ, Ziegler DS, Bautista F, et al. Phase 1b study of carfilzomib with induction chemotherapy in pediatric relapsed/refractory acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022;69(12):e29999.
If you participated in the study and have questions about the study results, the doctor or staff at your study center may be able to answer them.REC name
London - Central Research Ethics Committee
REC reference
15/LO/1226
Date of REC Opinion
28 Sep 2015
REC opinion
Further Information Favourable Opinion