RITUXIMAB for Follicular lymphoma

Inclusion criteria

• {"criterion_text":"- Follicular lymphoma grade I, II and IIIa according to the WHO classification. Re-biopsy at study entry is strongly encouraged but mandatory only in case of suspected transformation (elevated LDH or rapidly-growing disease or unusual relapse presentation)"}
• {"criterion_text":"- Be willing and able to comply with the protocol for the duration of the study."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Calculated creatinine clearances ≥ 40 ml/min."}
• {"criterion_text":"- All patients must agree to be using effective contraception for the entire treatment period according to standard guidelines for patients receiving lenalidomideFemales of childbearing potential (FCBP) must: - Have a negative medically supervised pregnancy test prior to starting of 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 and continued sexual abstinence. - Either commit to continued abstinence from heterosexual intercourse (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.  Male subjects must: - Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and for 28 days after discontinuation of study drug therapy. - Agree to not donate semen during study drug therapy and for 28 days after discontinuation of study drug therapy.  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 counselled about pregnancy precautions and risk of fetal exposure."}
• {"criterion_text":"- First or second relapse or progression following R-chemotherapy (Rituximab maintenance and IF radiotherapy are not considered treatment lines)."}
• {"criterion_text":"- Previous treatment with Bendamustine can be considered eligible if relapse occurred after ≥ 24 months."}
• {"criterion_text":"- Age >18 years"}
• {"criterion_text":"- Patients not eligible for high dose chemotherapy and ASCT because of: age ≥ 65 years, impaired PS or organ function due to major heart, lung, liver, kidney or other comorbidities or relapsed or refractory disease after previous ASCT."}
• {"criterion_text":"- stage II, III or IV according to Ann Arbor at relapse."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Must be able to adhere to the study visit schedule and other protocol standards."}
• {"criterion_text":"- ECOG performance status ≤ 2 (except when PS impairment is related to lymphoma)."}

Exclusion criteria

• {"criterion_text":"- Any lymphoma subtype other than FL including transformed FL"}
• {"criterion_text":"- Neuropathy > Grade 1."}
• {"criterion_text":"- Myocardial infarction within the last 6 months"}
• {"criterion_text":"- Presence or history of CNS involvement by lymphoma"}
• {"criterion_text":"- Subjects who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Total bilirubin > 2.0 mg/dl (34 umol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma"}
• {"criterion_text":"- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form."}
• {"criterion_text":"- Pregnant or lactating females"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Grade 3b follicular lymphoma"}
• {"criterion_text":"- Radiotherapy within 3 months prior to study entry"}
• {"criterion_text":"- Major surgery (excluding lymph node biopsy) within 28 days prior to registration."}
• {"criterion_text":"- 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 occult carriers 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."}
• {"criterion_text":"- Life expectancy < 6 months"}
• {"criterion_text":"- Known sensitivity or allergy to murine products"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Prior use of lenalidomide."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be the Progression-free Survival. PFS will be measured from the date of randomization to the date of documented first occurrence of disease progression or relapse or to the date of death from any cause. Patients without events considered and patients who are lost to follow up will be censored at their last assessment date.","definition_or_measurement_approach":"PFS measured from date of randomization to documented first occurrence of disease progression or relapse or death from any cause; patients without events or lost to follow-up are censored at last assessment date."}

Secondary endpoints

• {"endpoint_text":"- OS will be measured from the date of randomization and from enrolment to the date of death from any cause. Patients who have not died at the time of the final analysis will be censored at the date of the last contact.","definition_or_measurement_approach":"Overall survival measured from randomization/enrolment to death from any cause; survivors censored at last contact date."}
• {"endpoint_text":"- Toxicity will be classified according to definitions of Common Terminology Criteria for Adverse Event latest version (CTCAE). It will be determined by the incidence of severe, life- threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events (Infusion-related reactions).","definition_or_measurement_approach":"Toxicity classified per CTCAE latest version; incidence of CTCAE grade 3-5 and serious adverse events (including infusion-related reactions) will be determined."}
• {"endpoint_text":"- Rate of molecular remission will be defined as the proportion of patients PCR negative for Bcl-2/IgH at different time-points including those achieving continuous MR in two or more consecutive time-points.","definition_or_measurement_approach":"Proportion of patients PCR-negative for Bcl-2/IgH at specified time-points; includes those with continuous MR at ≥2 consecutive time-points."}
• {"endpoint_text":"- Rate of molecular conversion will be defined as the proportion of patients from baseline PCR-positivity to PCR-negativity.","definition_or_measurement_approach":"Proportion of patients converting from PCR-positive at baseline to PCR-negative."}
• {"endpoint_text":"- Rate of molecular relapse will be defined as the proportion of patients from PCR-negativity to PCR-positivity.","definition_or_measurement_approach":"Proportion of patients who convert from PCR-negative to PCR-positive (molecular relapse)."}
• {"endpoint_text":"- QoL will be measured at the baseline, the end of induction and at 6, 12 and 24 months of maintenance through the EORTC QLQ-C30 questionnaire.","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 at baseline, end of induction, and at 6, 12 and 24 months of maintenance."}

Italy

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

12-06-2025

Processing Time Days

476

Number Of Sites

29

Number Of Participants

160

Primary sponsor

Full Name

Fondazione Italiana Linfomi Ets

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Celgene Corporation (a Bristol Myers Squibb company)","duties_or_roles":"Monetary support","organisation_type":""}