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

Sponsor

CABYC (Industry)

Overall Status

Completed

CT.gov ID

NCT00505232

Collaborator

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea (Other)

Enrollment

Locations

Arm

63.9

Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma	Drug: Y-90 Ibritumomab tiuxetan	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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: 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.

Arm

Intervention/Treatment

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: 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.

Outcome Measures

Primary Outcome Measures

Treatment safety [36 months]
Safety of the treatment, recording the adverse events throughout the treatment.

Secondary Outcome Measures

Feasibility of proposed treatment scheme. [36 months]
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. [36 months]
Progression free, disease free and overall survivals. [36 months]
Analysis of the significance of the minimal residual disease (MRD) detection. [36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
2	Hospital Marques de Valdecilla	Santander	Cantabria	Spain	39008
3	Hospital del Mar	Barcelona	Cataluña	Spain	08003
4	Hospital Clinico de Valencia	Valencia	Comunidad Valenciana	Spain	46010
5	Hospital Dr. Peset	Valencia	Comunidad Valenciana	Spain	46017
6	Hospital Clínico de Santiago de Compostela	Santiago de Compostela	Galica	Spain	15705
7	Clinica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
8	Clinica Ruber	Madrid		Spain	28006
9	Hospital La Princesa	Madrid		Spain	28006
10	Clinica Moncloa	Madrid		Spain	28008
11	Hospital Ramon y Cajal	Madrid		Spain	28034
12	Hospital Universitario Puerta de Hierro	Madrid		Spain	28035
13	Hospital Universitario La Paz	Madrid		Spain	28046
14	Hospital Quiron	Madrid		Spain	28224
15	Hospital Morales Meseguer	Murcia		Spain	30008
16	Hospital Clínico de Salamanca	Salamanca		Spain	37007