A Phase III Multicenter, Randomized Study Comparing RIT Vs ASCT in Patients With Relapsed/Refractory (FL)
Relapsed Follicular Lymphoma
About this trial
This is an interventional treatment trial for Relapsed Follicular Lymphoma focused on measuring Relapsed follicular Lymphoma, RIT, Zevalin
Eligibility Criteria
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
Exclusion Criteria:
- Grade IIIb FL, transformed FL or histologies different from FL
- Previous treatment with > two lines of chemotherapy ± rituximab Maintenance is UNOTU considered a therapeutics line)
- Previous ASCT or RIT treatment
- CNS involvement by lymphoma
- HBV positivity with the exception of patients who are seropositive because of hepatitis B virus vaccination and patients HbcAb positive and HbsAg negative with undetectable serum HBV-DNA. Occult carriers: must receive treatment with Lamivudine 100 mg for the duration of treatment program and at least 12 months after treatment cessation; HBV-DNA levels and HBsAg will be monitored every month
- HCV positivity with elevated transaminases or INR or APTT or active virus replication
- HIV positivity
- Any concurrent medical condition requiring long term use (> one month) of systemic corticosteroids
- Active bacterial, viral, or fungal infection requiring systemic therapy
- Any concurrent medical or psychiatric condition which might impair administration of therapy or preclude the ability to give informed consent
- Treatment with an experimental agent within 30 days prior to study entry
- Myelosuppressive chemo or biological therapy within three weeks before study entry (use rituximab course delivered as maintenance is not an exclusion therapy)
- Major surgery other than diagnosis within 4 weeks prior to study entry
- Previous i.v. or i.m. treatments with murine or animal derived antibodies
Sites / Locations
- A.O.U. San Martino
- Ematologia, A.O. San Gerardo
- A.O. Niguarda
- IRCCS-Centro di riferimento oncologico UO di ematologia e Trapianto Cellule Staminali
- Azienda Ospedaliera "Bianchi Melacrino Morelli"
- Presidio Ospedaliero "A. Tortora"
- Emat Univ - Città della salute e della scienza di Torino
- Ospedale San Bortolo
- Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona
- A.O. SS. Antonio e Biagio e C. Arrigo
- Clinica di ematologia AOU Umberto I Ospedali Riuniti
- Ematologia con Trapianto Policlinico Universitario Consorziale
- Spedali Civili
- Presidio Ospedaliero A.Perrino - Divisione di Ematologia
- Divisione di Ematologia Osp. Businco
- IRCC Onco-Ematologia
- Ospedale Ferrarotto
- Policlinico Careggi Clinica Ematologica
- A O Papardo
- Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori
- IRCCS San Raffaele Unità di Chemioterapia
- Policlinico di Modena - Università degli studi
- Istituto Pascale Oncoematologia
- SCDU Ematologia - Università del Piemonte Orientale
- Ospedale S. Francesco
- Azienda Ospedaliera V. Cervello
- U.O. Complessa di Ematologia Ospedale di Parma
- Ematologia Policlinico San Matteo
- Ospedale Santa Maria della Misericordia
- Ospedale Santo Spirito Dipartimento di Ematologia
- Unità Ematologia Ospedale Civile di Piacenza
- Ausl Ravenna
- SC Ematologia AO Santa Maria Nuova IRCCS
- Univeristà La Sapienza
- SC Ematologia Città della salute e della scienza di Torino
- Filippo Gherlizoni
- UO Ematologia Osp. Cardinale Panico
- Clinica di Ematologia - A.O.U. S. Maria di Udine
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A RIT
ARM B ASCT
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). Zevalin® will be delivered as per indications and should thus be provided at expenses following regular supplies procedures.
BEAM conditioning regimen (or in alternative FEAM regimen with fotemustine to replace BCNU) and reinfusion of CD34+ cells of ≥ 2x106/Kg CD34+ day 0 (optimal dose to reinfuse 4x106/Kg CD34+). G-CSF 5 mcg/Kg from day 2 until ANC>1500/mmc. Patients who failed mobilization will directly proceed to rituximab maintenance