Phase II of Efficacy and Toxicity of Maintenance Sub. Rituximab After Induction in Relapsed MCL and Non-eligible HSCT

An Open Multicenter Phase II Study of Efficacy and Toxicity of Maintenance Subcut. Rituximab After Induction With Rituximab in Patients With Relapsed or Refractory Mantle-cell Lymphoma Non-eligible for HSCT

1. Primary endpoint: Time to relapse/progression (TTP) after achieving a complete or partial response with the (R-GemOxD)-induction therapy

2. Secondary endpoints:

   1. Quality of response obtained after subcutaneous Rituximab maintenance.
   2. Progression-Free Survival (PFS)
   3. Overall Survival (OS)
   4. Time to Next Therapy (TTNT)
   5. Value of MRD in the disease outcome
   6. Toxicity

This is a phase II trial evaluating the role of maintenance with subcutaneous Rituximab in patients with stage II-IV relapsed or refractory mantle-cell lymphoma with complete or partial response after the administration of a salvage regimen with R-GemOx-D.

Before the study start and in order to standardize the results, the same R-GemOx-D salvage regimen will be used: Rituximab: 375 mg/m2 on day 1, Gemcitabine: 1000 mg/m2 on day 2 (over 30 minutes) and Oxaliplatin: 100 mg/m2 on day 2 (over 3 hours), Dexamethasone 20 mg on day 1-3. Cycles should be repeated every 14 days, up to 8 cycles.

Patients who present a complete or partial response, after the salvage therapy, will start the study receiving subcutaneous Rituximab maintenance at dose of: 1400 mg every 2 months for 2 years; the study treatment will start 6-8 weeks after finishing the salvage therapy.

Patients will be evaluated every 2 months during treatment study phase and every 4 months in the follow up phase. More details in Appendix 1 (Schedule of Assessments)

Inclusion Criteria:

• Basal diagnosis of mantle-cell lymphoma in relapse or refractory.
• Achievement of a CR or PR after salvage therapy with R-GemOxD (6 to 8 cycles) as previously described4-5.
• Age > 18 years.
• One or maximum two prior chemotherapy or immunochemotherapy lines.
• Patients should not be considered candidates for high-dose chemotherapy and autologous stem-cell transplantation.
• No clinical evidence of CNS involvement
• Signed informed consent
• Serum creatinine less than 2 and/or bilirrubin less than 2.5 UNL.
• Pregnant or lactating woman. FCBP must agree to ongoing pregnancy testing during the course or study and commit to use effective contraception during the study

Exclusion Criteria:

• Prior organ transplantation.
• HIV positive.
• HBV related disease
• Any serious active disease or co-morbid medical condition (according to the investigator's decision)
• Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 cervix carcinoma.
• Less than 50% of tumor response.
• Platelet counts less than 50 x 109/L.
• Neutrophil counts less than 1.0 x 109/L.