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

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