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

This study has been completed.
Sponsor:
Collaborator:
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Information provided by (Responsible Party):
CABYC
ClinicalTrials.gov Identifier:
NCT00505232
First received: July 20, 2007
Last updated: December 30, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Y-90 Ibritumomab tiuxetan
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by CABYC:

Primary Outcome Measures:
  • Treatment safety [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    Safety of the treatment, recording the adverse events throughout the treatment.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: January 2006
Study Completion Date: May 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


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.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00505232

Locations
Spain
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
Hospital Quiron
Madrid, Spain, 28224
Hospital Universitario La Paz
Madrid, Spain, 28046
Clinica Moncloa
Madrid, Spain, 28008
Clinica Ruber
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
Sponsors and Collaborators
CABYC
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Investigators
Principal Investigator: Reyes Arranz, MD, PhD Hospital La Princesa
  More Information

No publications provided

Responsible Party: CABYC
ClinicalTrials.gov Identifier: NCT00505232     History of Changes
Other Study ID Numbers: GELTAMO-LCM-04-02, 2005-004400-37
Study First Received: July 20, 2007
Last Updated: December 30, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by CABYC:
Y-90 Ibritumomab tiuxetan
Rituximab
Hyper-CVAD
Mantle Cell Lymphoma Patients
Zevalin(R)

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Methotrexate
Rituximab
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 29, 2014