None listed
Conditions
Brief summary
This study aims to determine the safety and efficacy of treatment with either rituximab and lenalidomide or standard rituximab-containing chemotherapy, followed by rituximab alone in patients with previously untreated follicular lymphoma Who is it for? You may be eligible to join this study if you are aged at least 18 years and have been diagnosed with follicular lymphoma that is in need of treatment. You must have received no previous treatment for lymphoma. Trial details Upon entry to the trial, patients will be allocated to either rituximab and lenalidomide chemotherapy for 1.5 years, followed by 1 year of rituximab alone or standard rituximab containing chemotherapy for 6 months followed by 2 years of rituximab alone. Participants will be assessed at regular timepoints until the end of the trial to determine the safety and clinical benefit of the treatments. This Phase III study will: Investigate the survival benefit, the rate of remission, the time to disease relapse or next anti-lymphoma treatment, and safety of the patients allocated to each group and compare the groups to eachother.
Interventions
6 cycles of rituximab 375mg/m^2 on days 1,8,15,22 of cycle 1, day 1 of cycles 2-6 in conjunction with 20 mg daily oral lenalidomide on days 2-22 every 28 days.
Responding patients will continue to receive 375mg/m^2 rituximab intravenously (iv) every 8 weeks for 12 cycles together with a response adjusted dose of lenalidomide (patients exhibiting complete remission (CR) receive 12 cycles of 10mg daily on days 2-22 of 28 day cycles; patients exhibiting partial response (PR) receive an additional 3
6 cycles of rituximab 375mg/m^2 on days 1,8,15,22 of cycle 1, day 1 of cycles 2-6 in conjunction with 20 mg daily oral lenalidomide on days 2-22 every 28 days. Responding patients will continue to receive 375mg/m^2 rituximab intravenously (iv) every 8 weeks for 12 cycles together with a response adjusted dose of lenalidomide (patients exhibiting complete remission (CR) receive 12 cycles of 10mg daily on days 2-22 of 28 day cycles; patients exhibiting partial response (PR) receive an additional 3 or 6 cycles of 20 mg daily oral lenalidomide on days 2-22 every 28 days) until they achieve a CR, at which time they will continue to receive 10mg oral lenalidomide on days 2-22 of 28 day cycles for either 9 or 6 cycles. Patients who remain in PR will receive 10mg oral lenalidomide days 2-22 of 28 day cycles for the remaining 6 cycles.) All responding patients will receive a total of 18 cycles of lenalidomide. Patients who do not respond will be withdrawn from treatment.
Sponsors
The Lymphoma academic research organisation
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a as assessed by the investigators: 2. Have no prior systemic treatment for lymphoma. 3. Must be in need of treatment as evidenced by at least one of the following criteria: Bulky disease defined as: -a nodal or extranodal (except spleen) mass > 7cm in its greater diameter or, -involvement of at least 3 nodal or extranodal sites (each with a diameter greater than >3 cm) Presence of at least one of the following B symptoms: -fever (>38 degrees Celcius) of unclear etiology -night sweats -weight loss greater than 10% within the prior 6 months Symptomatic splenomegaly Compression syndrome (ureteral, orbital, gastrointestinal) Any one of the following cytopenias due to lymphoma: -hemoglobin < 10g/dL (6.25 mmol/L) -platelets <100 x 10^9/L , or -absolute neutrophil count (ANC) < 1.5 x 10^9/L Pleural or peritoneal serous effusion (irrespective of cell content) LDH> upper limit of normal (ULN) or beta 2 microglobulin > ULN 4. Bi-dimensionally measurable disease with at least one mass lesion > 2cm that was not previously irradiated. 5. Stage II, III or IV disease. 6. Must be > or = to 18 years and sign an informed consent. 7. Performance status less than or equal to 2 on the ECOG scale. 8. Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to signing informed consent, including: -Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L -Platelet count greater than or equal to 75 x 10^9/L -Hemoglobin greater than or equal to 8.0 g/dl (5 mmol/L) 9. Must be able to adhere to the study visit schedule and other protocol requirements. 10. Females of childbearing potential (FCBP) receiving lenalidomide must: -Have two negative pregnancy tests as verified by the study doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete abstinence from heterosexual contact. -Either commit to complete abstinence from heterosexual contact(which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy. 11. Male patients receiving lenalidomide must: Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy. Agree to not donate semen during study drug therapy and for 28 days after discontinuation of study drug therapy. 12. All patients receiving lenalidomide 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 study drug discontinuation. 13. For all patients receiving Rituximab: Women must not breast feed and must use effective contraception must not be pregnant and agree not to become pregnant during participation in the trial and during the 6 months thereafter. Men must agree not to father a child during participation in the trial and during the 6 months thereafter.
Exclusion criteria
1. Clinical evidence of transformed lymphoma by investigator assessment. 2. Grade 3b follicular lymphoma. 3. Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisolone (over these 4 weeks). 4. Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent. 5. Seropositive for or active viral infection with hepatitis B virus (HBV): -HBsAg positive -HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA Note: -Patients who are HBsAg negative, anti-HBs positive and/or anti HBc positive but viral DNA negative are eligible -Patients who are seropositive due to a history of hepatitis B vaccine are eligible. 6. Known seropositive for, or active infection hepatitis C virus (HCV). 7. Known seropositive for, or active viral infection with human immunodeficiency virus (HIV). 8. Life expectancy < 6 months. 9. Known sensitivity or allergy to murine products. 10. Prior history of malignancies, other than follicular lymphoma, unless the subject has been free of the disease for greater than or equal to 10 years. Exceptions include a history of previously treated: a. Localized non-melanoma skin cancer b. Carcinoma in situ of the cervix 11. Prior use of lenalidomide. 12. Neuropathy > Grade 1. 13. Presence or history of CNS involvement by lymphoma. 14. Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis. 15. Any of the following laboratory abnormalities: -serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) > 3x upper limit of normal (ULN), except in patients with documented liver or pancreatic involvement by lymphoma -total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma -creatinine clearance of < 30 mL/min 16. Uncontrolled intercurrent illness. 17. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 18. Pregnant or lactating females. 19. 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.
Outcome results
None listed