A Study of Two Associations of Rituximab and Chemotherapy, With a PET-driven Strategy, in Lymphoma

Hospices Civils de Lyon222 enrolled

Overview

This Phase II study randomized R-ACVBP and R-CHOP as induction treatment in patients from 18 to 59 with DLBCL CD20+ lymphoma and 2 or 3 adverse prognostic factors of the age-adjusted IPI. The consolidation treatment is allocated according to the response to induction treatment assessed by PET after the 2nd and 4th induction cycles.

1\) Induction Arm A: 4 cycles of R-ACVBP, 2 weeks interval. After the 3rd cycle, if PET 2+ (fixing), collection of peripheral blood stem cell progenitors will be organized at the time of hematological recovery under support with G-CSF. The consolidation treatment will depend on results of PET evaluation after cycle 2 (PET2) and cycle 4 (PET4). * Consolidation 1A (in case of PET 2- PET 4 -): * High-dose Methotrexate with folinic acid rescue; 2 cycles spaced out 14 days. * Rituximab-Ifosfamide-Etoposide : 4 cycles spaced out 14 days * Cytarabine sub-cutaneous, during 4 days; 2 cycles spaced out 14 days. * Consolidation 2 A (in case of PET 2+ PET4 -): * 2 cycles high-dose Methotrexate with folinic acid rescue * High dose with Z- BEAM conditioning regimen followed by autologous transplant. * Salvage(in case of PET 4 +): The patient will be treated with a salvage regimen, after a biopsy of the residual mass whenever possible. 2\) Induction arm B: 4 cycles of R-CHOP, 2 weeks interval. After the 3rd cycle, if PET 2+ (fixing), collection of peripheral blood stem cell progenitors will be organized at the time of hematological recovery under support with G-CSF. The consolidation treatment will depend on results of PET evaluation after cycle 2 (PET2) and cycle 4 (PET4). * Consolidation 1B(in case of PET 2- PET 4 -): 4 additional cycles of R-CHOP, 2-weeks interval * Consolidation 2 B(in case of PET 2+ PET 4 -): * 2 cycles high-dose Methotrexate with folinic acid rescue * High dose with Z- BEAM conditioning regimen followed by autologous transplant * Salvage(in case of PET 4 +): The patient will be treated with a salvage regimen, after a biopsy of the residual mass whenever possible

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

222

Conditions

Lymphoma, B-Cell Lymphoma, Large-Cell, Diffuse

Interventions

R-CHOP14 induction regimenDRUG

R-CHOP14 induction regimen

R-ACVBP14 induction regimenDRUG

R-ACVBP14 induction regimen

Eligibility

Sex: ALLMin age: 18 YearsMax age: 59 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification). * Age from18 to 59 years, eligible for transplant. * Patient not previously treated. * Baseline FDG-PET Scan (PET0) performed before any treatment with at least one hypermetabolic lesion. * Index prognostic factors (IPI) 2 or 3. * With a minimum life expectancy of 3 months. * Negative HIV, HBV and HCV serologies £ 4 weeks (except after vaccination). * Having previously signed a written informed consent. Exclusion Criteria: * Any other histological type of lymphoma. * Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included. * Central nervous system or meningeal involvement by lymphoma. * Contra-indication to any drug contained in the chemotherapy regimens. * Poor renal function (creatinin level \>150 mmol/l), poor hepatic function (total bilirubin level \>30 mmol/l, transaminases \>2.5 maximum normal level) unless these abnormalities are related to the lymphoma. * Poor bone marrow reserve as defined by neutrophils \<1.5 G/l or platelets \<100 G/l, unless related to bone marrow infiltration. * Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ)cervical carcinoma. * Any serious active disease (according to the investigator's decision). * Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy. * Pregnant or lactating women or women of childbearing potential not currently practicing an adequate method of contraception * Adult patient under tutelage. * Impossibility to performed a baseline PET scan (PET0) before randomization and treatment beginning

Locations (1)

René Olivier Casasnovas

Dijon, France

Outcomes

Primary Outcomes

Complete response rate after 4 inductive cycles with R-ACVBP14 or R-CHOP14, in DLBCL CD 20 (+) patients, presenting with 2 or 3 adverse prognostic factors of the aa-IPI Test a Pet-driven strategy Complete response rate after the 4 inductive cycles

Time frame: 4 inductive cycles with R-ACVBP14 or R-CHOP14

Secondary Outcomes

Response according to PET after 2 cycles, 4 cycles Induction toxicities Response duration Disease-, progression-, event-free and overall survival after autologous transplant Biological factors for prognosis Pharmacokinetic of rituximab

Time frame: 2 cycles and 4 cycles Induction

Data from ClinicalTrials.gov

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