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

NCT ID: NCT00505232

Last Updated: 2012-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2011-05-31

Brief Summary

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

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.

Conditions

Mantle Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab-HCVAD,Methotrexate/Cytarabine and Zevalin

Induction Treatment (Rituximab-HCVAD and Methotrexate/Cytarabine) followed by Consolidation Treatment (Rituximab and Y-90 Ibritumomab tiuxetan)

Group Type: EXPERIMENTAL

Y-90 Ibritumomab tiuxetan

Intervention Type: DRUG

Study Design

The present study will be split into two cohorts:

1. Patients younger than 60 years who will receive 8 chemotherapy cycles

2. 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.

Interventions

Y-90 Ibritumomab tiuxetan

Study Design

The present study will be split into two cohorts:

1. Patients younger than 60 years who will receive 8 chemotherapy cycles

2. 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

OTHER

Sponsor Role: collaborator

CABYC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Reyes Arranz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Locations

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Marques de Valdecilla

Santander, Cantabria, Spain

Hospital del Mar

Barcelona, Catalonia, Spain

Hospital Clínico de Santiago de Compostela

Santiago de Compostela, Galica, Spain

Clinica Ruber

Madrid, Madrid, Spain

Hospital La Princesa

Madrid, Madrid, Spain

Clinica Moncloa

Madrid, Madrid, Spain

Hospital Ramon y Cajal

Madrid, Madrid, Spain

Hospital Universitario Puerta de Hierro

Madrid, Madrid, Spain

Hospital Universitario La Paz

Madrid, Madrid, Spain

Hospital Quiron

Madrid, Madrid, Spain

Hospital Morales Meseguer

Murcia, Murcia, Spain

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Hospital Clínico de Salamanca

Salamanca, Salamanca, Spain

Hospital Clinico de Valencia

Valencia, Valencia, Spain

Hospital Dr. Peset

Valencia, Valencia, Spain

Countries

Spain

Other Identifiers

2005-004400-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GELTAMO-LCM-04-02

Identifier Type: -

Identifier Source: org_study_id