Patients aged 18-65 years with follicular lymphoma in first or second relapse MedDRA version: 14.1 Level: PT Classification code 10016905 Term: Follicle centre lymphoma, follicular grade I, II, III recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE MONOHYDRATE
CAS Number: 6055-19-2
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed I
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age 18-65; 2.Histologically documented diagnosis of grade I-IIIa FL defined according to WHO guidelines 2008 (Re-biopsy required); 3.Collection of BM and PB for MRD analysis; 4.Relapsed or refractory disease after = 2 chemotherapy lines at least one containing rituximab (rituximab maintenance is not considered a therapeutic line); 5.Clinical indication of systemic treatment i.e. Stage II-IV who require therapy according to SIE and GELF criteria; 6.ECOG performance status 0-2 (unless disease-related); 7.Availability of histological material for centralized revision; 8.Laboratory values: •ANC = 1500/mmc and/or platelets = 100000/mmc (unless due to marrow involvement by lymphoma) •Serum creatinine = 1.5 x ULN (unless disease-related) •bilirubin = 1.5 x ULN (or = 3.0 x ULN, if patient has Gilbert’s syndrome), AST/SGOT and/or ALT/SGPT = 2.5 x ULN if not disease related or = 5.0 x ULN in case of lymphoma liver involvement; 9.Adequate cardiac function: LVEF > 50% by echocardiography or MUGA scan; 10.Not pregnant or breast-feeding; 11.Willingness to use effective contraception during the study and 3 months after the end of treatment; 12.No other prior malignancies except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological finding of prostate cancer (TNM stage of T1a or T1b) or other cancer from which the patient has been disease-free for > 5 years; 13.Signed informed written consent. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 245 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1.Grade IIIb FL, transformed FL or histologies different from FL; 2.Previous treatment with > 2 lines of chemotherapy ± rituximab (rituximab maintenance is not considered a treatment line); 3.Previous ASCT or RIT treatment; 4.CNS involvement by lymphoma; 5.HBV positivity (except of patients HbcAb positive and HbsAg negative, HBV-DNA negative, provided lamivudine prophylaxis is given); 6.HCV positivity with active virus replication (HCV-RNA copies in serum), active hepatitis or impaired liver function. 7.HIV positivity; 8.Any concurrent medical condition requiring long term use (greater than one month) of systemic corticosteroids; 9.Active bacterial, viral, or fungal infection requiring systemic therapy; 10.Any concurrent medical or psychiatric condition which might impair administration of therapy or preclude the ability to give informed consent; 11.Treatment within an experimental agent within 30 days prior to study entry; 12.Myelosuppressive chemotherapy or biological therapy within three weeks before study entry (use rituximab course delivered as maintenance is not an exclusion therapy); 13.Major surgery other than diagnosis within four weeks prior to study entry.14.Previous i.v. or i.m. treatments with murine or animal derived antibodies.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare RIT with (90)Y Ibritumomab Tiuxetan (Zevalin) vs. ASCT in terms of PFS from randomization.;Secondary Objective: Secondary: 1.To compare OS; 2.To compare EFS from randomization and from enrollment and PFS from enrollment and TFS; 3.To compare CR rate and ORR; 4.To compare toxicity in both arms during induction, consolidation and maintenance; 5.To compare quality of life in both arms during treatment and follow-up; 6.To compare the cost-effectiveness of RIT vs. ASCT; 7.To compare the activity of RIT vs. ASCT on MRD assessed using the Bcl-2/IgH translocation in both nested PCR and real time quantitative PCR; 8.To assess the prognostic impact of MRD related parameters on PFS and OS.;Primary end point(s): PFS from randomization 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.;Timepoint(s) of evaluation of this end point: Three years from randomization (with 2 years of minimum follow up) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.OS will be measured from the date of randomization and from enrollment to the date of death from any cause; 2.PFS from enrolment 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; 3.EFS will be measured from the date of enrolment and from the date of randomization to the date of any treatment failure including death, disease progression or relapse, discontinuation of treatment for any reason (toxicity, patient preference, initiation of new treatment without documented progression); 4.TFS is defined for all patients who achieved a response (CR or PR) after the completion of consolidation phase as the time from the end of consolidation phase until the institution of the next chemotherapy; 5.CR Rate will be defined as the proportion of CR at the end of consolidation phase; 6.ORR will be defined as the proportion of CR or PR at the end of consolidation phase; 7.Safety 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) commencing during and up to 24 hours after the first drug infusion and at any time during therapy and follow-up; 8.QoL will be measured during the trial through the EORTC QLQ-C30 questionnaire; 9.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 EQ-5D questionnaire; 10.Rate of MR will be defined as the proportion of patients PCR negative for Bcl-2/IgH translocation after consolida | — |
Countries
Italy
Contacts
Public ContactSegreteria Scientifica
Fondazione Italiana Linfomi ONLUS
Outcome results
None listed