Treatment of lymphoma by Betalutin targeted internal radiation therapy

• Research type

  Research Study

• Full title

  A phase I/II study of 177Lu-HH1 (BetalutinTM) radioimmunotherapy for treatment of relapsed CD37+ non-Hodgkin lymphoma

• IRAS ID

  156193

• Contact name

  Bjørg Bolstad

• Contact email

  bb@nordicnanovector.no

• Sponsor organisation

  Nordic Nanovector AS

• Eudract number

  2011-000033-36

• Clinicaltrials.gov Identifier

  NCRN 3245, NCRN Number

• Duration of Study in the UK

  5 years, 6 months, 0 days

• Research summary

  Summary of Research
  This study involves patients that have relapsed non-Hodgkin's lymphoma. This is a disease that can be treated effectively with chemotherapy and immunotherapy, but relapses will occur, and there is therefore a need for new types of treatment. Antibodies with a radionuclide attached have previously proved to be effective in many cases (radioimmunotherapy). The purpose of this study is to test a new type of radioimmunotherapy in which the isotope Lutetium-177 is attached to the antibody HH1, which binds to cancer cells and normal white blood cells (leukocytes). This product is called Betalutin.

  This is a Phase 1/2 study which means that it never tested on humans before. In this stage the idea is to find the right dose that will be safe, most beneficial to the patient and with the minimum side effects. The study consists of 2 phases: a dose ­escalation phase (Phase 1) in which we find the right dose, and a cohort­ expansion phase (Phase 2) where we test the determined dose.

  The UK will participate in Phase 2 of the study. Phase 1 is in progress and will be completed by centres in Norway and Sweden.

  There is a screening phase, a treatment phase, and a follow up phase in this study.
  patients will receive a single treatment of Betalutin and receive regular testing for the first 3 months, this is the treatment phase. They will then be followed up every 3 months up to 1 year, then every 6 months for a further 4 years.

  Patients will stay on study until the meet any of the withdrawal criteria. Patients may withdraw consent at any time.

  Summary of Results
  The study results were separated into 3 parts A, B and C. Part A was composed of an early analysis of trial results.

  Part A:
  What were the overall results from the study?
  Nine out of the first 32 participants tested with the various treatment combinations at the start of the study reported side effects considered to be a possible limitation for tolerating Betalutin. The key limitations were drops in neutrophils (another type of white blood cells that fight infection) and drops in platelets (a part of the blood which forms clots to stop bleeding). There were also delays in neutrophil levels recovering and bleeding due to low levels of platelets.

  Based on the overall safety information of Betalutin in these participants, two of the treatment combinations were chosen to be tested in bigger groups of participants:
  1. 40 mg lilotomab then 15 MegaBequerel Betalutin (tested in 30 extra participants) 2. 100 mg/ lilotomab then 20 MegaBequerel* Betalutin (tested in 12 extra
  participants)
  
  The researchers took scans of parts of the body before the start of treatment and at regular timepoints afterwards to evaluate if the Non-Hodgkin’s lymphoma had shrunk, stayed the same, or grown. Participants finished the main part of the study when their tumour grew or if they started another Non-Hodgkin’s lymphoma treatment. The study staff contacted participants by telephone afterwards to find out if they were still alive.

  The early results from Part A indicated that Betalutin may be effective in patients with a particular type of Non-Hodgkin’s lymphoma called follicular lymphoma.

  The researchers found that the tumours shrank in:
  • 16 out of the 25 participants with follicular lymphoma who got 40 mg lilotomab then 15 MegaBequerel Betalutin (called “40/15”) • 11 out of the 16 participants with follicular lymphoma who got 100 mg/m 2 lilotomab then 20 MegaBequerel* Betalutin (called “100/20”) • 10 out of the 16 participants with follicular lymphoma who got other treatment combinations of Betalutin • 8 out of the 17 participants with types of non-Hodgkin’s lymphoma other than follicular lymphoma

  Side effects are medical events (such as headache) that happen during the study and are reported because the study doctor believes that they might be related to the treatments in the study. A side effect is considered “serious” if it results in death, is a life-threatening condition, is considered to be medically important by the study doctor, causes long-term problems, needs hospital care or makes current hospital care longer.

  There were 2 participants who received rituximab pre-treatment but then had to leave the study. Both participants were able to re-enter the study at a later date so have been counted twice. The side effects in this section are therefore based on a total of 76 participants, as the participants who re-entered the study are counted twice.

  Did any participants have serious side effects?
  A total of 7 of the 76 participants had serious side effects. These were:
  
  Number of Participants (%)*
  Irregular and fast heart rate: 2 participants (3%) Drop in platelets: 2 participants (3%) Low levels of neutrophils and infection: 1 participant (1%)
  Pneumonia: 1 participant (1%)
  Sepsis (blood poisoning): 1 participant (1%) Pharyngitis (sore throat):1 participant (1%) Drop in neutrophils: 1 participant (1%) Chronic myelomonocytic leukaemia (type of blood cancer): 1 participant (1%) Nose bleed: 1 participant (1%) *Participants could have more than one side effect Neutrophils are types of white blood cells that take part in the body’s immune response. Platelets are cells in the blood involved in clotting.

  A total of 25 participants died during the 5-year study, none of them died due to a side effect of the treatment.

  Did any participants have non-serious side effects?
  Non-serious side effects happened in 80% of the participants. This was 61 of the 76 participants. The non-serious side effects below happened in 5 or more participants. There were other non-serious side effects, but these happened in fewer participants.

  Number of Participants (%)*
  Abnormally low levels of neutrophils: 27 participants (36%) Abnormally low levels of platelets: 23 participants (30%) Drop in white blood cells: 20 participants (26%) Drop in neutrophils: 16 participants (21%) Abnormally low white blood cell count: 15 participants (20%) Drop in platelets: 14 participants (18%) Drop in lymphocytes: 12 participants (16%) Abnormally low lymphocyte count: 11 participants (15%) Nausea (feeling sick): 6 participants (8%) Anaemia (low number of red blood cells): 5 participants (7%) Fatigue (tiredness): 5 participants (7%) *Participants could have more than one side effect Lymphocytes and neutrophils are types of white blood cells that take part in the body’s immune response. Platelets are cells in the blood involved in clotting.

  How has this study helped researchers?
  This study has helped researchers start to learn about Betalutin as a possible treatment for people living with Non-Hodgkin’s lymphoma.

  Part B and C of this study were reported separately. New studies with Betalutin are not currently planned. Further studies may be performed in the future, including studies looking at the effect of Betalutin when given with standard treatments for Non-Hodgkin’s lymphoma.

  Part B and C:

  What were the overall results from the study?
  The researchers took scans of parts of the body before the start of treatment and at regular timepoints afterwards to evaluate if the lymphoma had shrunk, stayed the same, or grown. Participants finished the main part of the study when their tumour grew or if they started another lymphoma treatment. The study staff contacted participants by telephone afterwards to find out if they were still alive.

  The researchers found that the tumours shrank in:
  • 28 out of the 72 participants with follicular lymphoma who got 40 mg lilotomab then 15 Megabequerel Betalutin (called “40/15”)
  • 9 out of the 28 participants with follicular lymphoma who got 100 mg/m2 lilotomab then 20 Megabequerel Betalutin (called “100/20”)

  What side effects happened during the study?
  Side effects are medical events (such as headache) that happen during the study and are reported because the study doctor believes that they might be related to the treatments in the study. A side effect is considered “serious” if it results in death, is a life-threatening condition, is considered to be medically important by the study doctor, causes long-term problems, needs hospital care or makes current hospital care longer.

  Did any participants have serious side effects?
  There were 11 serious side effects in 10 participants assessed to be related to Betalutin: radiation pneumonitis (inflammation of the lungs caused by radiation therapy), blood poisoning, ruptured bowel, fever associated with a drop in neutrophils in 2 participants, pneumonia, tooth abscess, feeling unwell, shingles, myelodysplastic syndrome (a type of cancer where blood cells in the bone marrow do not become healthy blood cells) and uterine cancer.

  Did any participants have non-serious side effects?
  Some of the participants had non-serious side effects. At least one non-serious side effect happened in 94 of the 113 participants that received lilotomab and Betalutin. The most common (occurring in 10 or more participants) were:

  Number of Participants (%)*
  Drop in platelets: 25 participants (22%) Drop in neutrophils: 17 participants (15%) Anaemia (low red blood cells): 10 participants (9%) Fatigue (tiredness): 10 participants (9%) *Participants could have more than one side effect

  How has this study helped researchers?
  This study has helped researchers start to learn about Betalutin as a possible treatment for people living with relapsed or refractory Non-Hodgkin’s lymphoma, including follicular lymphoma.
  New studies with Betalutin are not currently planned. Further studies may be performed in the future.

• REC name

  HSC REC B

• REC reference

  14/NI/1037

• Date of REC Opinion

  1 Aug 2014

• REC opinion

  Further Information Favourable Opinion