Study of combination of rituximab and lenalidomide treatment in patients with recurrent or unresponsive indolent (slow growing) lymphoma who have been treated previously
- Conditions
- Relapsed/refractory indolent lymphomaMedDRA version: 20.0Level: LLTClassification code 10060707Term: MALT lymphomaSystem Organ Class: 100000004864MedDRA version: 20.0Level: HLTClassification code 10041650Term: Splenic marginal zone lymphomasSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10029461Term: Nodal marginal zone B-cell lymphomasSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10016903Term: Follicle centre lymphomas, follicular grade I, II, IIISystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001245-14-PT
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
- Age =18 years at the time of signing the ICD
- Understand and voluntarily sign an ICD prior to any study related assessments/procedures are conducted.
- Histologically confirmed marginal zone lymphoma or follicular lymphoma (grade 1, 2 or 3a)
- Previously treated with at least one prior systemic chemotherapy, immunotherapy or chemoimmunotherapy: and must have received at least 2 previous doses of rituximab
a) Systemic therapy does not include, for example:
i. Local involved field radiotherapy for limited stage disease
ii. H. Pylori eradication
b) Prior investigational therapies will be allowed provided the subject has received at least one prior systemic therapy as discussed in a)
- Documented relapsed, refractory or progressive disease after treatment with systemic therapy, and must not be rituximab-sensitive if had received rituximab or R-chemoregimen therapy refractory
a) Relapsed lymphoma: replapsed after initial response of CR to prior therapy.
b) Progressive lymphoma: PD after initial response of PR or SD to the prior therapy.
c) Refractory limphoma: Subject who received a non-rituximab containing systemic therapy and who experienced the best response of PD to this therapy is considered to have refrectory lymphoma.
d) Rituximab-refractoriness is defined as:
i. Did not respond (at least a PR) to rituximab or R-chemoregimen therapy and/or
ii. Time to disease progression < 6 months after last rituximab dose.
e) Rituximab-sensitive MZL or FL defined as
i. Responded (at least a PR) to rituximab or R-chemoregimen therapy and
ii. Time to disease progression = 6 months after last rituximab dose
f) Subjects with gastric MALT lymphoma and evidence of H. pylori (HP) infection must have documented non-response to antibiotic therapy as judged by a minimum follow up of 12 months after successful HP-eradication
- Investigator considers rituximab monotherapy appropriate
- Bi-dimensionally measurable disease
- Must be able to adhere to the study visit schedule and other protocol requirements
- Eastern Cooperative Oncology Group (ECOG) Performance status = 2
- Fulfilled laboratory requirements
- Willingness to follow pregnancy precautions
- All subjects must: Have an understanding that the study drug could have a potential teratogenic risk; agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of study drug therapy; agree not to share study medication with another person; agree to be counseled about pregnancy precautions and risk of fetal exposure; females must agree to abstain from breastfeeding during study participation and for at least 28 days after lenalidomide/placebo discontinuation and according to the approved rituximab product/prescribing information.
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 105
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 245
- Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma
- Subjects taking corticosteroids during the last week, unless administered at a dose equivalent to = 20 mg/day prednisone or prednisolone
- Major surgery (excluding lymph node or bone marrow biopsy) within 28 days prior to signing informed consent
- Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 8 weeks or use of radioimmunotherapy within 6 months
- Known seropositive for or active viral infection with hepatitis B virus (HBV), human immunodeficiency virus (HIV)
- Known seropositive for or active infection with hepatitis C virus (HCV)
- Hepatitis C virus (HCV) positive subjects with chronic HCV hepatitis or subjects with an active HCV infection requiring anti-viral medication (at time of randomization). (HCV positive subjects who do not have active treatment, as documented by the investigator, are eligible. The infection or unacceptable liver damage as documented by one of the following options: liver ultrasound for fibrosis, liver biopsy, zero RNA viral load, or other local practice test.
- Life expectancy < 6 months
- Known sensitivity or allergy to murine products
- Presence or history of central nervous system involvement by lymphoma
- Subjects who are at a risk for a thromboembolic event and are not willing to take prophylaxis for it
- Prior use of lenalidomide
- Known allergy of thalidomide
- Neuropathy > Grade 1
- Uncontrolled intercurrent illness
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- Pregnant or lactating females
- Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that 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 Main Objective: To compare the efficacy of rituximab plus lenalidomide to rituximab plus placebo in subjects with relapsed/refractory indolent lymphoma.;Secondary Objective: •To compare the safety of rituximab plus lenalidomide versus rituximab plus placebo <br>•To compare the efficacy of rituximab plus lenalidomide versus rituximab plus placebo using other parameters of efficacy:<br> -Durable complete response rate (DCRR), overall response rate (ORR), duration of response (DoR) and duration of complete response (DoCR) by IWG 2007 without PET.<br> -OS, EFS, time to next anti-lymphoma treatment (TTNLT).;Primary end point(s): Progression-free survival (PFS), as assessed by the IRC using the 2007 IWG criteria.;Timepoint(s) of evaluation of this end point: Years 1-3: Every 12 weeks (±1 week); <br>Year 4: Every 16 weeks (±1 week); <br>Year 5 onwards: Every 6 months (± 2 weeks). <br>Assessments will be performed until progression or relapse
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Durable complete response rate (DCRR)<br>• Overall Survival (OS), Overall Response Rate (ORR), Complete Response Rate (CR Rate), Duration of Response (DoR), Duration of Complete Response (DoCR), Event-Free Survival (EFS), Time to Next anti-Lymphoma Treatment (TTNLT), Safety<br><br>;Timepoint(s) of evaluation of this end point: Years 1-3: Every 12 weeks (±1 week);<br>Year 4: Every 16 weeks (±1 week); <br>Year 5 onwards: Every 6 months (± 2 weeks). <br>Response assessments will be performed until progression or relapse with continued follow-up for survival and second primary malignancies up to 5 years from last subject randomized.