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)
Conditions
Interventions
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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
Exclusion criteria
Exclusion criteria: - 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate in patients responsive to induction whether the R2-MANT program may improve progression-free survival (PFS) compared to patients treated with R-MANT.;Secondary Objective: To compare in patients respondents to induction the R2-MANT vs the R-MANT program for: - Safety, in terms of rate of grade III-IV adverse events. - Efficacy, in terms of OS. To evaluate the activity of maintenance program on MRD assessed in terms of: rate of conversion to molecular remission, rate of molecular relapse, disease kinetics by real time PCR in the bone marrow (BM) and peripheral blood (PB). To assess the prognostic impact of molecular persistence and relapse on PFS and OS. To assess quality of life (QoL) at study entry and to compare QoL between study arms at the end of induction and at 6, 12 and 24 months of maintenance , using the EORTC QLQ-C30C questionnaire. To compare the cost-effectiveness of treatment arms by performing a detailed analysis of direct medical costs including chemotherapy, lenalidomide, patient monitoring, management of side effects and relapses through the evaluation of total healthcare costs and QALYs using (EQ-5D) questionnaire. ;Primary end point(s): The primary endpoint will be the Progression-free Survival. PFS will be measured from the date of randomisation 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.;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - OS will be measured from the date of randomisation 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. - PFS will be measured from the date of enrolment 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. - Toxicity will be classified according to definitions of Common Terminology Criteria for Adverse Event version 4.03 (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). - 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. - Rate of molecular conversion will be defined as the proportion of patients from baseline PCR-positivity to PCR-negativity. - Rate of molecular relapse will be defined as the proportion of patients from PCR-negativity to PCR-positivity. - 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. - The incremental cost-effectiveness ratio (ICER) will be calculated by dividing the difference in mean total costs between the two arms by the difference in the mean effects. The ICER will be calculated for the primary clinical effect measures of the trial. (i.e. PFS) and for QALYs. QALYs will be calculated multiplying the amount of time a patient spent in a particular health state by the utilities estimated using the Euro-Qol (EQ-5D) questionnaire. ;Timepoint(s) of evaluation of this end point: 64 months | — |
Countries
Italy
Contacts
Public ContactSecretary
FONDAZIONE ITALIANA LINFOMI ONLUS
Outcome results
None listed