FIL FLAZ12

A phase III multicenter, randomized study comparing consolidation with (90)Yttrium-Labeled Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy vs Autologous Stem Cell Transplantation (ASCT) in patients with relapsed/refractory follicular lymphoma (FL) aged 18-65 years

Objectives, structure and design of the Study

Study design

Multicenter open label phase III randomized trial

STEP I: Induction

Three courses standard dose rituximab-chemotherapy (R-CHOP, R-DHAP, R-FM, R-ICE, R-IEV or R-Bendamustine)

STEP II: Randomization

Patients achieving at least PR will be randomized either to RIT (arm A) or ASCT (arm B)

STEP III: Stem cell mobilization

All patients will receive Ara-C and rituximab, followed by stem cell collection (aim of collecting 6x106 CD34+ cells/kg) A second mobilization with plerixafor will be allowed for patients that experience a mobilization failure after Ara-C (both arms).

STEP IV: Consolidation

• ARM A (RIT): infusion of 90Y Ibritumomab Tiuxetan if the patient has less than 25% BM infiltration at the pre-consolidation restaging.
• ARM B (ASCT): BEAM conditioning regimen (or in alternative FEAM regimen) and reinfusion of CD34+ cells. G-CSF until ANC>1500/mmc.

STEP V: Maintenance

Rituximab every three months for eight courses to all patients (starting three months after consolidation).

STEP VI: Follow-up Phase

The follow-up phase will continue until month 36 from randomization or until study end.

Primary objective

To compare RIT with (90)Y Ibritumomab Tiuxetan (Zevalin®) vs. ASCT in terms of PFS from randomization.

Secondary objectives

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 Bcl2/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;
9. To assess feasibility, toxicity and efficacy (in terms of ORR, PFS and OS) of delivering ASCT after failure of RIT.

Clinical phase

III

Indication

Patients aged 18-65 years with follicular lymphoma in first or second relapse, or with refractory disease.

Sample size

265 patients will be enrolled in order to randomize 210 patients (80%) at the end of the induction phase

Number of Centers and location of the Study

60 Centers

Study duration

5 years based on the following assumption:

• 3 years of accrual
• 2 years of follow-up after entry of the last patient

Study start date

April 2012