Phase 3 Blinatumomab in Paediatric Subjects With B-precursor ALL
Research type
Research Study
Full title
A Randomized, Open-label, Controlled Phase 3 Adaptive Trial to Investigate the Efficacy, Safety, and Tolerability of the BiTE Antibody Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects With High-risk First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
IRAS ID
176792
Contact name
Donna Lancaster
Contact email
Sponsor organisation
AMGEN Research (Munich) GmbH
Eudract number
2014-002476-92
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 1 months, 5 days
Research summary
In this research, blinatumomab or standard of care chemotherapy will be provided as part of a treatment regimen to children and adolescents with high-risk first relapse B-precursor acute lymphoblastic leukemia. Acute lymphoblastic leukemia is a cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cells) and normal blood cell development in the marrow is inhibited.
Summary of Results
This summary shows the main results from one clinical study. The results are only for this 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.
Some information in this summary may be different from the approved labelling for blinatumomab. Your healthcare professional should refer to the full prescribing information for proper use of blinatumomab.
2. Who Sponsored This Study?
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 USA Phone (United States): 1 805-447-1000 Amgen Inc. is the sponsor of the study and makes blinatumomab, the medicine tested in the study. Amgen would like to thank everyone who participated in this study and feels it is important to share the results of this study.3. General Information About the Clinical Trial
• This study took place in 13 countries.
• The study began in November 2015 and ended in November 2022.
• The study stopped accepting participants as the main aim of the study was met sooner than expected.Blinatumomab is an immunotherapy medicine that is used for the treatment for children and adolescents with B-precursor acute lymphoblastic leukemia (B-ALL), a type of cancer of the white blood cells. Blinatumomab is approved for use in children or adolescents. Blinatumomab helps the immune system (the body’s defense against infections) to find and destroy cancer cells.
This was a phase 3 study, the late stage of the development process of medicines for humans. Researchers compared blinatumomab to standard chemotherapy treatment used for B-ALL. The main purpose of the study was to compare how long participants survived without B-ALL returning or failing to improve, or being diagnosed with a second cancer.
4. Who Was Included in This Study?
This study included 111 children and adolescents with B-ALL. 53 participants (48%, or about 48 out of 100) were boys and 58 participants (52%, or about 52 out of 100) were girls. At the start of the study, these participants ranged in age from
1 to 17 years; 80 participants (72%, or about 72 out of 100) were 9 years of age or younger, and 31 participants (28%, or about 28 out of 100) were at least 10 years old.
This study took place at 48 study centers across 13 countries. The numbers of participants in each country are shown below.Participants were examined by a study doctor and chosen to be in the study if they met certain requirements. Participants had to be older than 28 days and younger than 18 years when the study started. A chromosome refers to a part of the cell that passes genes from parent to child. The Philadelphia chromosome is an abnormal chromosome that is sometimes found in leukemia cells. Participants in this study did not have the Philadelphia chromosome. Additionally, participants had B-ALL that had returned after initially improving with a prior treatment, and was likely to get worse. Participants in this study also had abnormal numbers of lymphoblasts, a type of immature white cell, in their bone marrow (M1 if lymphoblasts in bone marrow were less than 5%, M2 if lymphoblasts in bone marrow were between 5% and 25%).
5. Which Medicines Were Studied?
This was an open-label study, which means that the participants, their parents/guardians, and the study doctors knew which treatment the participants received. The participants, their parents/guardians, and the study doctors could not choose the study medicine the participants received. Participants were put into a treatment group by chance (“randomized”). This is like flipping a coin or drawing numbers out of a hat.
Blinatumomab and standard chemotherapy were the medicines evaluated in this study. Blinatumomab and standard chemotherapy were given through a needle into the vein (also referred to as intravenous or IV). The blinatumomab dose was
15 μg/m2/day (15 micrograms per square meter of body surface area per day) given as a continuous infusion over 4 weeks.
The standard chemotherapy treatment included a combination of 6 IV medications (dexamethasone, vincristine, daunorubicin, methotrexate, ifosfamide, and pegylated-asparaginase) given in a cycle of 1 week of treatment followed by 3 weeks without treatment.Following the study treatment with either blinatumomab or standard chemotherapy, participants had a stem cell transplant, which is another treatment for B-ALL. Overall, this study included a screening period of up to 3 weeks (when the study doctor checked to see if the participant met the inclusion and exclusion criteria for the study), a 4-week treatment period, a 1-week safety follow-up period, a 12-month short-term follow-up period, and a long-term follow-up period of at least 36 months.
111 participants joined the study:• 54 participants were randomized to blinatumomab; all 54 participants started treatment and 2 participants did not complete the treatment.
• 57 participants were randomized to standard chemotherapy; 52 of the 57 participants started treatment and 3 of the 52 participants who started treatment did not complete the treatment.The figure below shows what happened during the study.
6. What Were the Side Effects?
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(s). These possible side effects are listed below.
The table below shows how many participants had side effects.Side Effects During the Study
Blinatumomab (54 participants), Chemotherapy (52 participants)How many participants had serious side effects? Blinatumomab 9 participants (17%), Chemotherapy 15 participants (29%) How many participants had non-serious side effects? Blinatumomab 45 participants (83%), Chemotherapy 40 participants (77%)
How many participants died from side effects? Blinatumomab 0 participants (0%), Chemotherapy 0 participants (0%)
How many participants stopped taking the study medicine because of side effects? Blinatumomab 2 participants (4%), Chemotherapy 0 participants (0%)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. No participant died due to a side effect.
The table below shows the serious side effects that occurred in at least 2 participants (4%).Serious Side Effects During the Study
Blinatumomab (54 participants), Chemotherapy (52 participants)Serious side effect
Seizure: Blinatumomab 2 participants (4%), Chemotherapy 0 participants (0%) Problems with the nervous system: Blinatumomab 2 participants (4%), Chemotherapy 0 participants (0%) Low white blood cell count with fever: Blinatumomab 0 participants (0%), Chemotherapy 6 participants (12%) Low white blood cell count: Blinatumomab 0 participants (0%), Chemotherapy 2 participants (4%) Sores and inflammation in mouth: Blinatumomab 0 participants (0%), Chemotherapy 2 participants (4%) Low platelet count (part of the blood that helps clotting): Blinatumomab 0 participants (0%), Chemotherapy 2 participants (4%)The table below shows the non-serious side effects that occurred in at least 10% of participants (or about 10 out of 100).
Non-serious Side Effects During the Study Blinatumomab (54 participants), Chemotherapy (52 participants)
Non-serious side effect
Fever: Blinatumomab 29 participants (54%), Chemotherapy 2 participants (4%)
Headache: Blinatumomab 10 participants (19%), Chemotherapy 1 participant (2%)
Low red blood cell count: Blinatumomab 2 participants (4%), Chemotherapy 19 participants (37%)
Low white blood cell count: Blinatumomab 1 participant (2%), Chemotherapy 11 participants (21%) Sores and inflammation in mouth: Blinatumomab 1 participant (2%), Chemotherapy 20 participants (38%) Low platelet count (part of the blood that helps clotting): Blinatumomab 1 participant (2%), Chemotherapy 9 participants (17%) Platelet count decreased on blood test (part of the blood that helps clotting): Blinatumomab 0 participants (0%), Chemotherapy 7 participants (13%)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?
• Researchers monitored participants to find out when certain “events” occurred. These “events” included the return of their cancer, their cancer not improving, being diagnosed with a second cancer, or if they passed away. Researchers measured the amount of time it took from when a participant started in the study to when an event occurred. The researchers then put the times for all participants in a treatment group in order from lowest to highest. The number that is in the exact middle of the list of numbers (the “median”) is chosen and is called the “median event free survival”. This study found that in the participants who received standard chemotherapy, the median event free survival was 7.8 months. In the blinatumomab group, median event free survival could not be determined. This means that some participants in that group had not yet experienced an “event” (return of their cancer, their cancer not improving, being diagnosed with a second cancer, or passing away) and would need to be followed for longer to determine the median event free survival.
• Overall, 39% of participants (21 out of 54 participants) in the blinatumomab group had either died, had their cancer return or not improve, or were diagnosed with a second cancer by the end of the study. In the standard chemotherapy group, 65% of participants (37 out of 57 participants) had either died, had their cancer return or not improve, or were diagnosed with a second cancer by the end of the study.
• This study stopped accepting participants as the main aim of the study was met sooner than expected.
• The researchers determined that the differences seen between the groups were not likely due to chance.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
111 children and adolescents with B-ALL. Not all participants in the 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?
If more clinical studies are done, they may be listed on public websites, such as those below. Search for blinatumomab on the websites below
The purpose of this research is to see if blinatumomab is safe in children and adolescents with high-risk first relapse B-precursor acute lymphoblastic leukemia and whether it causes any side effects.
This research will also look to see if blinatumomab effectively eliminates tumour cells from the body in children and adolescents.
Blinatumomab is still experimental and is not approved by any regulatory health agency (like the Food and Drug Administration [FDA] or European Medicines Agency [EMA]) for use in children and adolescents with high-risk first relapse B-precursor acute lymphoblastic leukemia.
A total of about 202 children and adolescents are expected to participate in this research. It will take place in approximately 60 centres in Europe, Israel and Australia.
After previously receiving induction therapy and standard of care chemotherapy, participation in this study will be randomly assigned to either one cycle of blinatumomab or one block of standard of care chemotherapy.
Blinatumomab will be administered as a continuous intravenous (IV) infusion via a mini pump that can be carried by the participant (in a shoulder or beltbag
with the pump and infusion bag) for 4 weeks. Depending on the participants overall condition, continuous infusion of blinatumomab may be given on an outpatient basis, so study participants may leave the hospital with the pump, if determined to be safe and feasible.Participation in this study can be up to 38 months including the expected duration of study drug administration as well as any long-term follow-up visits/contacts.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
15/EM/0543
Date of REC Opinion
3 Feb 2016
REC opinion
Further Information Favourable Opinion