A randomized phase III multicenter trial assessing efficacy and toxicity of a combination of Rituximab and Lenalidomide (R2) vs Rituximab alone as maintenance after chemoimmunotherapy with Rituximab-Bendamustine for relapsed/refractory FL patients not eligible for autologous transplantation (ASCT)
- Conditions
- Maintenance following R-chemotherapy (Rituximab-Bendamustine) of patients with follicular lymphoma in first or second relapse or progression and not eligible for autologous stem cell transplantation (ASCT)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2012-003392-18-IT
- Lead Sponsor
- FONDAZIONE ITALIANA LINFOMI ONLUS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
- Follicular lymphoma grade I, II and IIIa according to the WHO classification. Availability of archival diagnostic biopsy for histological revision. Rebiopsy at study entry is strongly encouraged but mandatory only in case of suspected transformation (elevated LDH or rapidly-growing disease or unusual relapse presentation) or if archival diagnostic biopsy is not available.
- First or second relapse or progression following R-chemotherapy (Rituximab maintenance and IF radiotherapy are not considered treatment lines).
- Patients not eligible for more curative approaches i.e high dose chemotherapy and ASCT.
- Age >18 years.
- Stage II, III or IV according to Ann Arbor at relapse.
- Need of treatment according to SIE-SIES-GITMO guidelines for follicular lymphoma: stage II-IV with systemic symptoms, high tumor burden (i.e. >3 lymph nodes measuring >3 cm or a single lymph node >7 cm), extranodal disease, cytopenia due to marrow involvement, spleen involvement (=16 cm by CT), leukemic phase, serious effusion, symptomatic or life endangering organ involvement, rapid lymphoma progression, consistently increased LDH levels.
- Must be able to adhere to the study visit schedule and other protocol standards.
- ECOG performance status = 2 (except when PS impairment is related to lymphoma).
- Be willing and able to comply with the protocol for the duration of the study.
- Absolute neutrophil count (ANC) = 1.5 x 10 9/L unless due to marrow involvement by lymphoma; and platelets count = 75 x 109/L unless due to marrow involvement by lymphoma.
- Calculated creatinine clearances = 40 ml/min.
- Agree to be using effective contraception for the entire treatment period according to standard guidelines for patients receiving lenalidomide.
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 213
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
- Any lymphoma subtype other than FL including transformed FL
- Grade 3b follicular lymphoma.
- Radiotherapy within 3 months prior to study entry
- Subjects regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks).
- Major surgery (excluding lymph node biopsy) within 28 days prior to registration.
- HIV positive serology. HBV and HCV positive patients will be not excluded from the study if the hepatic enzymes are within the ranges later defined. HBV positive patients will be given lamivudine as prophylaxis starting one week before chemotherapy. HbsAg, HBcAb, HBV-DNA and HCV-RNA levels will be monitored twice every month in HCV or HBV positive patients.
- Life expectancy < 6 months.
- Known sensitivity or allergy to murine products.
- Prior history of malignancies, other than follicular lymphoma, unless the subject has been free of the disease for > 3 years with the exception of adequately cured localized non-melanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast or incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
- Prior use of lenalidomide.
- Neuropathy > Grade 1.
- Myocardial infarction within the last 6 months
- Presence or history of CNS involvement by lymphoma.
- Subjects who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis.
- Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) > 3x upper limit of normal (ULN), except in subjects with documented liver involvement by lymphoma
- Total bilirubin > 2.0 mg/dl (34 umol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma
- Uncontrolled intercurrent illness.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or lactating females.
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.
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