Safety Study to Evaluate Induction and Consolidation Treatment in Patients With Mantle Cell Lymphoma (LCM-04-02)

Study Overview
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Brief Summary
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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.

Detailed Description
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Study Design: 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.

Official Title
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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

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Y-90 Ibritumomab tiuxetan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All histologic MCL subtypes (WHO classification) Age between 18 and 70 years old Performance status 0 to 2 (ECOG) Cardiac ejection fraction >50% Adequate organ (hepatic, cardiac and renal) and marrow function: Hb> 10g/dl, neutrophil counts> 1500/ µl, platelet> 100000/ µl. Creatinine < 2,5xULN, bilirubin, AST or ALT<2,5xULN. For Y90-ibritumomab tiuxetan administration: Bone Marrow Infiltration by lymphoma cells < than 25% ; platelet count >100,000/µl and neutrophil counts >1500/µl Informed consent should be obtained Exclusion Criteria: Ann Arbor stages I or II without B symptoms or bulky disease (>10 cm). Previous chemotherapy or radiotherapy treatment. Uncontrolled current illness: Hepatic, renal, cardiovascular, neurological or metabolic illness. Symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia. HIV, HBV or HCV positive serology. Limitation of the patient´s ability to comply with the treatment or follow-up protocol. Men and women with reproductive potential who are not using effective contraceptive methods during and at least 12 months after the end of the study Acute or chronic active infection. Known hypersensitivity to some of the drugs or other related compounds No informed consent obtained

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab-HCVAD,Methotrexate/Cytarabine and Zevalin<br>Induction Treatment (Rituximab-HCVAD and Methotrexate/Cytarabine) followed by Consolidation Treatment (Rituximab and Y-90 Ibritumomab tiuxetan) | Drug: Y-90 Ibritumomab tiuxetan<br>* Study Design The present study will be split into two cohorts: Patients younger than 60 years who will receive 8 chemotherapy cycles Patients older than 60 years who will receive 6 chemotherapy cycles 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment safety | Safety of the treatment, recording the adverse events throughout the treatment. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of proposed treatment scheme. | Number and percentage of patients susceptible of receiving consolidation treatment after induction chemotherapy, according to inclusion criteria for consolidation with radioinmunotherapy. | 36 months | 
| Efficacy based on response rate: overall, partial and complete response. |  | 36 months | 
| Progression free, disease free and overall survivals. |  | 36 months | 
| Analysis of the significance of the minimal residual disease (MRD) detection. |  | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Y-90 Ibritumomab tiuxetan, Rituximab, Hyper-CVAD, Mantle Cell Lymphoma Patients, Zevalin(R)