Relapsed Follicular Lymphoma
Conditions
Keywords
Relapsed follicular Lymphoma, RIT, Zevalin
Brief summary
This is a Phase III, multicenter, open-label, randomized and controlled study to compare the efficacy of a consolidation therapy with RIT versus ASCT in patients with FL in CR or PR after second or third line chemotherapy supplemented with rituximab.
Detailed description
This is a Phase III, multicenter, open-label, randomized and controlled study to compare the efficacy of a consolidation therapy with RIT vs. ASCT in patients with FL in CR or PR after second or third line chemotherapy supplemented with rituximab. Patients with FL will be eligible for screening at the time of relapsed or refractory disease after two or less chemotherapy lines at least one containing rituximab. This study will be conducted in six steps as follows. Screening Phase, Enrolment and Induction chemotherapy (STEP I) Randomization (STEP II) Stem cell mobilization and collection (STEP III) Consolidation (RIT vs ASCT) (STEP IV) Maintenance (STEP V) Follow-up Phase (STEP VI)
Interventions
OTHERZEVALIN
Infusion of 90Y Ibritumomab Tiuxetan if the patient has less than 25% BM infiltration at the pre-consolidation restaging (0.4 mCi/kg if platelets ≥150,000/mmc, 0.3 mCi/kg if platelets are between 100.000 and 150,000/mmc).
DRUGBEAM
BEAM REGIMEN day -6 Carmustine\* 300 mg/ m2 i.v. in 250ml dextrose 5% solution from day -5 to day -2 Cytarabine 200 mg/m2 i.v. every 12 hours in 250 ml dextrose 5% solution, 250 ml/hr Etoposide 100 mg/m2 i.v. every 12 hours in 250 ml dextrose 5% solution, 250 ml/hr day -1 Melphalan 140 mg/m2 i.v. in 100ml saline solution in 200 ml/hr day 0 UReinfusion of autologous stem cells following this rules: 1. Patient collecting ≥6x106 CD34+ cells/kg use \>4x106 CD34+ cells/kg for ASCT and keep \>2x106 CD34+ cells/kg for back up; 2. Patient collecting 4-6x106 CD34+ cells/kg use \>2x106 CD34+ cells/kg for ASCT and keep \>2x106 CD34+ cells/kg for back up; 3. Patient collecting 2-4x106 CD34+ cells/kg use all CD34+ cells for ASCT and keep no back up. day 2 Filgrastim or Lenograstim 5μg/Kg s.c. until ANC \> 1500/mmc
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 * Histologically documented diagnosis of grade I-IIIa FL defined according to WHO guidelines 2008 (Re-biopsy required) * Availability of BM and PB for Minimal Residual Disease (MRD) analysis (see Appendix I) * Relapsed or refractory disease after ≤ two chemotherapy lines at least one containing Rituximab (Rituximab maintenance is UNOTU considered a therapeutic line) * Clinical indication of treatment i.e. Stage II-IV who require therapy according to SIE and GELF criteria (see Appendix II) * ECOG performance status 0-2 (unless disease-related) (see Appendix III) * Availability of histological material for centralized revision * Laboratory values: * ANC ≥ 1500/mmc unless due to marrow involvement by lymphoma and/or platelets ≥ 100000/mmc unless due to marrow involvement by lymphoma * Serum creatinine ≤ 1.5 x ULN, unless it is disease related * Bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome) * AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN if not lymphoma related or ≤ 5.0 x ULN in case of lymphoma liver involvement * Adequate cardiac function: LVEF \> 50% by echocardiography or MUGA scan * Not pregnant or breast-feeding * Willingness to use effective contraception during the study and 3 months after the end of treatment * No other prior malignancies except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for ≥ 5 years (see
Exclusion criteria
14) * Signed informed written consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival from randomization (rPFS) | 36 months | PFS will be defined as the time between the date of randomization and the date of disease progression, relapse or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival from randomization (rOS) | 36 months | OS will be defined as the time between the date of randomization and the date of death from any cause. |
| Event Free Survival (EFS) | 36 months | EFS will be measured 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). |
| Treatment Free Survival from randomization (TFS) | 36 months | TFS will be defined as the time between the date of the end of primary treatment until the institution of the next unplanned chemotherapy in randomized population. |
| Progression Free Survival from enrolment (ePFS) | 42 months | PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause. |
| Overall Survival from enrolment (eOS) | 42 months | OS will be defined as the time between the date of enrolment and the date of death from any cause |
| Complete Response (CR) Rate | At the end of the consolidation phase (6 months) | Proportion of CR according to the Cheson 2007 response criteria at the end of consolidation phase. |
| Overall Response Rate (ORR) | At the end of the consolidation phase (6 months) | ORR at the end of the consolidation phase is defined as Complete Response (CR) or Partial Response according to the Cheson 2007 response criteria. |
| Toxicity | 42 months | Incidence of grade 3 or higher Toxicity measured by CTCAE v.4.03 during therapy. |
| Molecular Response rate (MR) | 36 months | Rate of MR will be defined as the proportion of patients achieving PCR negativity after the consolidation phase and during follow up. |
| Molecular Response rate conversion (cMR) | 6 months | Rate of conversion will be defined as the proportion of patients with baseline PCR-positivity converting to PCR-negativity during treatment. |
| Molecular Relapse Rate (MRR) | 24 months | Rate of molecular relapse will be defined as the proportion of patients with PCR-negativity after treatment converting to PCR-positivity during the first two years of follow-up. |
Countries
Italy
Contacts
PRINCIPAL_INVESTIGATORUmberto Vitolo
AO Città della salute e della Scienza di Torino - Ospedale S. Giovanni Battista - TORINO
PRINCIPAL_INVESTIGATORMarco Ladetto
AO SS. Antonio e Biagio e Cesare Arrigo Alessandria
Outcome results
None listed