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

Mantle Cell Lymphoma Clinical Trial

— LCM-04-02  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00505232
• Other study ID #: GELTAMO-LCM-04-02
• Secondary ID: 2005-004400-37
• Status: Completed
• Phase: Phase 2
• First received: July 20, 2007
• Last updated: December 30, 2011
• Start date: January 2006
• Est. completion date: May 2011

Study information

• Verified date: December 2011
• Source: CABYC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: May 2011
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• Y-90 Ibritumomab tiuxetan
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.

Locations

Country	Name	City	State
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital del Mar	Barcelona	Cataluña
Spain	Clinica Moncloa	Madrid
Spain	Clinica Ruber	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Quiron	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Morales Meseguer	Murcia
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico de Santiago de Compostela	Santiago de Compostela	Galica
Spain	Hospital Clinico de Valencia	Valencia	Comunidad Valenciana
Spain	Hospital Dr. Peset	Valencia	Comunidad Valenciana

Sponsors (2)

Lead Sponsor	Collaborator
CABYC	Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment safety	Safety of the treatment, recording the adverse events throughout the treatment.	36 months	Yes
Secondary	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	No
Secondary	Efficacy based on response rate: overall, partial and complete response.		36 months	No
Secondary	Progression free, disease free and overall survivals.		36 months	No
Secondary	Analysis of the significance of the minimal residual disease (MRD) detection.		36 months	No