Clinical trial NCT00505232: Safety Study to Evaluate Induction and Consolidation Treatment in Patients With Mantle Cell Lymphoma (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Y-90 Ibritumomab tiuxetan
Rituximab
Hyper-CVAD
Mantle Cell Lymphoma Patients
Zevalin(R)
Lead sponsor: CABYC
Sponsor class: INDUSTRY
Collaborators: name: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
First posted: 2007-07-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Treatment safety
timeFrame: 36 months
Secondary outcomes:
measure: Feasibility of proposed treatment scheme.
timeFrame: 36 months
measure: Efficacy based on response rate: overall, partial and complete response.
timeFrame: 36 months
measure: Progression free, disease free and overall survivals.
timeFrame: 36 months
measure: Analysis of the significance of the minimal residual disease (MRD) detection.
timeFrame: 36 months
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Hospital Dr. Peset
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago de Compostela
state: Galica
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Clinica Ruber
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Clinica Moncloa
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Quiron
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
Study officials:
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: Reyes Arranz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: