Treatment of lymphoma with targeted internal radiation therapy(Betalutin)
- Conditions
- on-Hodgkin B-cell lymphomaPart A: Relapsed indolent Non-Hodgkin B-cell lymphomaPart B: Relapsed follicular lymphomaPart C: Relapsed indolent Non-Hodgkin B-cell lymphomaMedDRA version: 22.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-000033-36-DK
- Lead Sponsor
- ordic Nanovector ASA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 200
Part A (phase I and phase IIa) and Part C (phase IIa Pharmacokinetic
Cohort):
1. Histologically confirmed (by WHO classification) relapsed incurable non-Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA (for Part C, this excludes patients meeting Part B criteria, who should enter Part B), marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.
2. Age = 18 years.
3. Part A: A pre-study WHO performance status of 0-1; Part C: WHO performance status of 0-2.
4. Life expectancy should be = 3 months.
5. <25% tumour cells in bone marrow biopsy (biopsy taken from a site not previously irradiated).
6. Measurable disease by radiological methods.
7. Women of childbearing potential must:
a) understand that the study medication is expected to have teratogenic risk.
b) have a negative pregnancy test.
c) agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea.
8. Male subjects must agree to use condoms during intercourse throughout study drug therapy and the following 12 months.
9. Patients previously treated with native rituximab are eligible.
10. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination.
11. The patient has been fully informed about the study and has signed the informed consent form.
Part B:
1. Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (grade I-IIIA).
2. Male or female aged = 18 years.
3. Received at least 2 prior systemic anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy). Systemic regimens including agents such as idelalisib or other PI3K inhibitors qualify as a prior line of therapy.
4. Prior therapy must have included rituximab/anti-CD20 agent and an alkylating agent – which may be been administered in separate
regimens.
5. Patients must be refractory any at least one previous regimen that contained rituximab or an anti-CD20 agent, with refractoriness defined as
i. no response (no CR or PR) during therapy, or
ii. a response (CR/PR) lasting less than 6 months after the completion of a regimen including rituximab/anti-CD20 therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20 maintenance therapy, or within 6 months of completion of maintenance therapy).
6. WHO performance status of 0-2.
7. Life expectancy of = 3 months.
8. Bone marrow tumour infiltration < 25% (in biopsy taken from a site not previously irradiated).
9. Measurable disease by CT or MRI: longest diameter (LDi) > 1.5 cm for nodal lesion, LDi > 1.0 cm for extra nodal lesion on an assessment
performed during the screening period.
Criteria 10 and 11 must be satisfied within 72 hours of the
administration of rituximab:
10. ANC = 1.5 x 109/L.
11. Platelet count = 100 x 109/L .
Criteria 12 to 15 must be verified at time of eligibility review within 2
weeks prior to rituximab administration:
12. Haemoglobin = 9.0 g/dL.
13. Total bilirubin =1.5 x upper limit of normal (ULN) (except patients with documented Gilbert’s syndrome [< 3.0 mg/dL]).
14. Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or ALP = 2.5 x ULN (or = 5.0 x ULN with liver involvement by primary disease).
15. Adequate renal function as demon
Part A (phase I and phase IIa) and Part C (phase IIa Pharmacokinetic Cohort)
1. Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, uncontrolled asthma/allergy requiring systemic steroids, known HIV positive
2. Laboratory values within 15 days pre-registration:
a. Absolute Neutrophil Counts (ANC) = 1.5 x 109 /l
b. Part A: Platelet count = 150 x 109 /L. Part C: Platelet count <150×109/L
For Part C, criteria 2a and 2b must be satisfied within 72 hours of the administration of rituximab
c. Total bilirubin = 30 mmol/l (Part A only)
Total bilirubin > 1.5×ULN (except patients with documented Gilbert's syndrome [=3.0 mg/dL]) (Part C only)
d. ALP and ALAT = 4x normal level (Part A only)
Aspartate transaminase (AST), ALT or ALP >2.5×ULN (or >5.0×ULN with liver involvement by primary disease) (Part C only)
e. Creatinine = 115 µmol/l (men), 97 µmol/l (women) (Part A only)
Serum creatinine =1.5×ULN (Part C only)
f. Haemoglobin <9.0 g/dL (Part C only)
3. Known CNS involvement of lymphoma
4. Previous total body irradiation
5. Positive test for HAMA at screening
6. Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study treatment. Pre-treatment with rituximab is allowed
7. Pregnant or lactating women
8. Previous hematopoietic stem cell transplantation (autologous and allogenic)
9. Part A: Previous treatment with radioimmunotherapy. Part C: Not applicable
10. Actively participating in another study or received an investigational drug within 4 weeks prior to enrolment
11. Receipt of live, attenuated vaccine within 30 days prior to enrolment
12. Part A and Part C: Test positive for hepatitis B (HBsAg and anti-HBc). Part C only: Test positive for hepatitis C and HIV
13. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab or Betalutin
Part B (FL phase IIb)
1. Prior hematopoietic allogenic stem cell transplantation
2. Patients with a prior autologous stem cell transplanted (SCT) are excluded unless at least two years have elapsed since transplantation
3. Evidence of histological transformation from FL to diffuse large B-cell lymphoma (DLBCL) at time of screening (transformation to grade IIIB
that was successfully treated with recurrence of grade I-IIIA initial clone is accepted)
4. Previous total body irradiation
5. Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other systemic agent including any investigational agent) within 4 weeks prior to start of study treatment (corticosteroid treatment at doses of = 20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor [G-CSF] or granulocytemacrophage colony-stimulating factor [GM-CSF] are permitted up to 2 weeks prior to start of rituximab)
6. Patients who are receiving any other investigational medicinal products
7. Patients with known or suspected CNS involvement of lymphoma
8. History of malignancy other than FL within 5 years prior to screening,(i.e. patients with cancer diagnosed within 5 years prior to screening or who were diagnosed prior to 5 years and were not in CR or were on treatment within 5 years prior to screening), with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method