A Phase III Multicenter, Randomized Study Comparing RIT Vs ASCT in Patients With Relapsed/Refractory (FL)

Prior treatment

• Previous treatment with \> two lines of chemotherapy ± rituximab Maintenance is UNOTU considered a therapeutics line)
• Previous ASCT or RIT treatment
• Any concurrent medical condition requiring long term use (\> one month) of systemic corticosteroids
• 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

Other illness

• HIV positivity
• Active bacterial, viral, or fungal infection requiring systemic therapy

Lab values

• 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

Other

• Grade IIIb FL, transformed FL or histologies different from FL
• CNS involvement by lymphoma

• 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