Safety Study to Evaluate Induction and Consolidation Treatment in Patients With Mantle Cell Lymphoma (LCM-04-02)
Mantle Cell Lymphoma (MCL) is a malignancy with a poor response to treatment and with a median survival of 2- 4 years since diagnosis. Although histology is similar to that of an indolent lymphoma, MCL is currently considered an aggressive tumour. Few prospective therapeutic trials have been reported in MCL, and results are difficult to interpret due to treatment heterogeneity. It is known that standard chemotherapy for other clinically aggressive lymphomas yields poor results. Recently, better results have been communicated with intense induction chemotherapy treatments or consolidating the response with high dose chemotherapy with stem cell support. Keeping in mind these considerations, we will use and intensive induction treatment with Hyper-CVAD/MTX-AraC associated with anti-CD20 in order to increase the overall response rate followed by consolidation treatment with Ibritumomab -tiuxetan (Zevalin) with the aim of eradicate the minimal residual disease, responsible of relapse.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Induction Treatment With Anti-CD20 Plus Hyper-CVAD and Methotrexate/Cytarabine Followed by Consolidation Treatment With Y90 Ibritumomab-Tiuxetan in Patients With Mantle Cell Lymphoma|
- Treatment safety [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]Safety of the treatment, recording the adverse events throughout the treatment.
- Feasibility of proposed treatment scheme. [ Time Frame: 36 months ] [ Designated as safety issue: No ]Number and percentage of patients susceptible of receiving consolidation treatment after induction chemotherapy, according to inclusion criteria for consolidation with radioinmunotherapy.
- Efficacy based on response rate: overall, partial and complete response. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Progression free, disease free and overall survivals. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Analysis of the significance of the minimal residual disease (MRD) detection. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2006|
|Study Completion Date:||May 2011|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Experimental: Rituximab-HCVAD,Methotrexate/Cytarabine and Zevalin
Induction Treatment (Rituximab-HCVAD and Methotrexate/Cytarabine) followed by Consolidation Treatment (Rituximab and Y-90 Ibritumomab tiuxetan)
Drug: Y-90 Ibritumomab tiuxetan
The present study will be split into two cohorts:
The induction schema summarises as follows :
Anti-CD20/Hyper -CVAD chemotherapy will be alternated with anti-CD20 +MTX/Ara-C chemotherapy twice. Afterward, response will be evaluated, followed by, either, four cycles further patients younger than 60 years who will obtain a CR or PR, or 2 cycles patients older than 60 y. (see figure 1 and flow chart).
Consolidation treatment will consist in a single dose of Y90-Ibritumomab -Tiuxetan (Zevalin) [0.4 mCi/Kg b.w or 0.3 mCi/kg if platelets < 100,000/µl] will be administered 8 to 12 weeks after last chemotherapy.
- The Patients will receive 6 cycles of induction chemotherapy as follows: Anti-CD20/Hyper -CVAD chemotherapy will be alternated with anti-CD20 +MTX/Ara-C chemotherapy. After 4 cycles (2 x2), response will be evaluated. If response (complete or partial) is observed, 2 additional cycles will be administrated. If less than a partial response is observed, the patient will be out of the study.
- Consolidation treatment will be a single dose of Y90Ibritumomab -Tiuxetan (Zevalin) will be administered after 12 weeks after completion of induction chemotherapy. The initial dose of Zevalin will be 0.3 mCi/kg, to be further escalated to 0.4 mCi/Kg if unacceptable toxicity does not occur.
|Hospital Germans Trias i Pujol|
|Badalona, Barcelona, Spain, 08916|
|Hospital Marques de Valdecilla|
|Santander, Cantabria, Spain, 39008|
|Hospital del Mar|
|Barcelona, Cataluña, Spain, 08003|
|Hospital Clinico de Valencia|
|Valencia, Comunidad Valenciana, Spain, 46010|
|Hospital Dr. Peset|
|Valencia, Comunidad Valenciana, Spain, 46017|
|Hospital Clínico de Santiago de Compostela|
|Santiago de Compostela, Galica, Spain, 15705|
|Clinica Universitaria de Navarra|
|Pamplona, Navarra, Spain, 31008|
|Hospital Ramon y Cajal|
|Madrid, Spain, 28034|
|Madrid, Spain, 28224|
|Hospital Universitario La Paz|
|Madrid, Spain, 28046|
|Madrid, Spain, 28008|
|Madrid, Spain, 28006|
|Hospital La Princesa|
|Madrid, Spain, 28006|
|Hospital Universitario Puerta de Hierro|
|Madrid, Spain, 28035|
|Hospital Morales Meseguer|
|Murcia, Spain, 30008|
|Hospital Clínico de Salamanca|
|Salamanca, Spain, 37007|
|Principal Investigator:||Reyes Arranz, MD, PhD||Hospital La Princesa|