LNH2007-3B: A Study of Two Associations of Rituximab and Chemotherapy, With a PET-driven Strategy, in Lymphoma

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT00498043

Collaborator

(none)

222

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell Lymphoma, Large-Cell, Diffuse	Drug: R-CHOP14 induction regimen Drug: R-ACVBP14 induction regimen	Phase 2

Detailed Description

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.

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 Design

Study Type:

Interventional

Actual Enrollment :

222 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase II Study of Two Associations of Rituximab and Chemotherapy, With a PET -Driven Strategy, in Patients From 18 to 59 With DLBCL CD20+ Lymphoma and 2 or 3 Adverse Prognostic Factors of the Age-adjusted IPI

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-CHOP-14 R-CHOP14 induction regimen	Drug: R-CHOP14 induction regimen R-CHOP14 induction regimen
Experimental: R-ACVBP14 R-ACVBP14 induction regimen	Drug: R-ACVBP14 induction regimen R-ACVBP14 induction regimen

Arm

Intervention/Treatment

Experimental: R-CHOP-14

R-CHOP14 induction regimen

Drug: R-CHOP14 induction regimen

R-CHOP14 induction regimen

Experimental: R-ACVBP14

R-ACVBP14 induction regimen

Drug: R-ACVBP14 induction regimen

R-ACVBP14 induction regimen

Outcome Measures

Primary Outcome Measures

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 [4 inductive cycles with R-ACVBP14 or R-CHOP14]

Secondary Outcome Measures

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 [2 cycles and 4 cycles Induction]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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