Non-Hodgkin's Follicular and Non-Follicular indolent lymphomas, relapsed/refractory MedDRA version: 16.0 Level: LLT Classification code 10051812 Term: Small cell lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.0 Level: PT Classification code 10003908 Term: B-cell small lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version
Conditions
Interventions
Trade Name: Arzerra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OFATUMUMAB
CAS Number: 679818-59-8
Current Sponsor code: NA
Other descriptive name: NA
Concentration
Sponsors
Istituto Clinico Humanitas - Humanitas Cancer Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent obtained according to local guidelines 2. Histologically documented diagnosis of grade I-II-IIIa follicular lymphoma or defined according to WHO guidelines 2008. Re-biopsy suggested if transformation to aggressive subtype is suspected OR histologically documented indolent non follicular lymphoma: small lymphocytic lymphoma, lymphoplasmacytoid/lymphoplasmacytic lymphoma, Waldenstrom macroglobulinemia, nodal marginal zone lymphoma 3. Relapsed or refractory disease after >=1 chemotherapy lines, at least one rituximab-containing. Both patients with rituximab–sensitive and rituximab-refractory disease in any previous line are admitted. Refractoriness to rituximab is defined as no objective response or documented progression within 6 months of a) receiving the first dose of a full-course single agent rituximab or b) completion of rituximab maintenance therapy or progression before the next rituximab dose or c) completion of a full course rituximab in combination with chemotherapy . Previous high dose therapy and autologous stem cell transplantation (ASCT) is also admitted. Previous allogeneic transplantation is excluded. 4. Age >= 18 years 5. ECOG performance status 0-2 6. Locally available histological material 7. Clinical indication for treatment as determined by the investigator 8. No prior treatment with bendamustine and/or ofatumumab 9. Measurable disease by CT scan 10. Life expectancy of at least 3 months 11. Laboratory values: · Absolute neutrophil count (ANC) = 1.5 x 109/L unless due to marrow involvement by lymphoma - In this case patient can be included upon physicians’s decision · Platelet count : = 100 x 109/L unless due to marrow involvement by lymphoma. In this case patient can be included upon physicians’s decision · Serum creatinine within normal range · Serum total bilirubin = 1.5 x ULN (or = 3.0 x ULN, if patient has Gilbert syndrome), unless due to lymphoma involvement of the liver. In case of liver involvement, patient can be included upon physicians’s decision. · AST/SGOT and ALT/SGPT = 2.5 x upper limit of normal (ULN) or = 5.0 x ULN if the transaminase elevation is due to disease involvement of the liver · alkaline phosphatase = 2.5 times ULN (unless due to disease involvement of the liver or bone). In case of liver or bone involvement, patient can be included upon physicians’s decision 12. Adequate cardiac function : LVEF > 50% through echocardiography or MUGA scan 13. Resolution of all acute toxic effects (excluding alopecia) of any prior therapy to NCI CTCAE (Version 4.03) Grade = 1 14. Not pregnant or nursing 15. Negative pregnancy test 16. Fertile patients must use effective contraception during the study and 3 months after the end of treatment. 17. Negative HIV test 18. No other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for = 5 years unless approved by the Sponsor Principal Investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 49 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. Diagnosis of mucosa associated marginal zone lymphoma, splenic marginal lymphoma or chronic lymphocytic leukaemia 2. Evidence of histological transformation to an aggressive histological subtype 3. Previous allogeneic stem cell transplantation 4. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement by lymphoma or stable chronic liver disease per investigator assessment) 5. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study. 6. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 1 month prior to start the therapy 7. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C (see below). 8. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae 9. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. 10. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. 11. Any concurrent medical condition requiring long term use (> 1 month) of systemic corticosteroids 12. Any concurrent medical or psychiatric condition which might impair administration of therapy or preclude the ability to give informed consent 13. Known hypersensitivity to study drugs, mannitol, or any excipients 14. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded. HBV DNA –negative cases can be included provided that HBV monitoring is performed during treatment and follow up period. 15. Positive serology for hepatitis C (HC) defined as a positive test for HCVAb, in which case reflexively perform a HCVRNA test to confirm the result. Cases with no signs of active chronic hepatitis (= HCV RNA NEG) are admitted. 16. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence. 17. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Ofatumumab in combination with Bendamustine in previously treated (>=1 chemotherapy lines, at least one rituximab-containing) indolent follicular and non follicular non Hodgkin’s lymphomas.;Secondary Objective: - To further characterize the efficacy profile of Ofatumumab-Bendamustine in combination (duration of response, time to next treatment, progression free survival and overall survival, minimal residual disease in follicular lymphoma subtypes). - To evaluate safety;Primary end point(s): Overall response rate (CR+ PR) defined as per Cheson criteria.;Timepoint(s) of evaluation of this end point: Response will be evaluated during treatment, at the end of treatment and during follow up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Toxicities as outlined in NCI-CTCAE version 4.03, Duration of response defined for patients in CR or PR, Time to Next Treatment, progression free survival, overall survival, MRD evaluation in FL patients only and correlation with PFS and OS.;Timepoint(s) of evaluation of this end point: During treatment and follow up. | — |
Countries
Italy
Contacts
Public ContactU.O. Oncologia ed Ematologia
Istituto Clinico Humanitas - Humanitas Cancer Center
Outcome results
None listed