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

Lymphoma, B-Cell Clinical Trial

— LNH2007-3B  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00498043
• Other study ID #: 2007.462
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2007
• Last updated: August 12, 2014
• Start date: July 2007
• Est. completion date: October 2013

Study information

• Verified date: August 2014
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 59 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• R-CHOP14 induction regimen
R-CHOP14 induction regimen
• R-ACVBP14 induction regimen
R-ACVBP14 induction regimen

Locations

Country	Name	City	State
France	René Olivier Casasnovas	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes

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