Rituximab, Gemcitabine and Oxaliplatin (R-GEMOX) for Refractory/Relapsed B-cell Lymphoma

Diffuse Large Cell Lymphoma Clinical Trial

Official title:

Gemcitabine-oxaliplatin Plus Rituximab (R-GEMOX) in Refractory/Relapsed Patients With CD 20 Positive Diffuse Large B-cell Lymphoma, Non Eligible for High-dose Chemotherapy Followed by Autotransplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00169195
• Other study ID #: R-GEMOX
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: September 1, 2015
• Start date: April 2003
• Est. completion date: November 2012

Study information

• Verified date: September 2015
• Source: Lymphoma Study Association
• 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

The Purpose of this study is to evaluate the efficacy and the safety of R-GEMOX in refractory/relapsed patients with CD20-positive large B-cell lymphoma who are not eligible for autologous transplantation.

Description:

This is a multicentric, open-label, non-randomized clinical study, evaluating the efficacy and the safety of R-GEMOX in refractory/relapsed patients aged from 18 to 75 years with CD20-positive large B-cell lymphoma non eligible for autologous transplantation.

It is anticipated that 50 subjects will be enrolled over 4 years (from April 2003/January 2007), but inclusion could stop earlier according to the analysis performed every 5 patients (based on triangular test).

The duration of the treatment period is approximately 16 weeks and patients are followed until death.

The total duration of the study is expected to be 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed with histologically or cytologically proven, CD 20+, diffuse large B-cell lymphoma,

• Relapse after first or second CR, PR or less than PR to first-line treatment for the rituximab-naïve patients, OR relapse after first or second CR with a minimum delay of 12 months between the last rituximab infusion and the inclusion for the rituximab-experienced patients

• Aged 18 - 75 years

• Not eligible for autologous transplantation

• Previously treated with chemotherapy containing anthracycline, with or without rituximab

• ECOG performance status 0 to 2

• With a minimum life expectancy of 3 months

• Having signed informed consent form prior to enrollment

Exclusion Criteria:

• Burkitt's, mantle cell, T-cell lymphomas

• CD 20-negative lymphoma

• HIV or HBV related disease

• Central nervous system or meningeal involvement by the lymphoma

• Not previously treated with anthracycline-containing regimens

• Contraindication to any drug contained in the R-GEMOX chemotherapy regimen

• Any serious active disease or co-morbid medical condition (according to the investigator's decision),

• Poor renal function (creatinine level > 150micromol/l), poor hepatic function (total bilirubin level > 30mmol/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

• Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study

• Any radiotherapy during the four weeks before inclusion

• Pregnant or lactating woman

• Adult patient unable to give informed consent because of intellectual impairment.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Gemcitabine-Oxaliplatin plus Rituximab (R-GEMOX)

Locations

Country	Name	City	State
France	Hôpital Henri Mondor	Créteil
France	Service d'Hématologie Clinique - CHU Le Bocage	Dijon
France	Service des Maladies du Sang - CHRU de Lille	Lille
France	Centre Léon Bérard	Lyon
France	Hôpital Saint Louis	Paris
France	Service D'Hématologie Adulte - Hôpital Necker	Paris
France	Centre Henri Becquerel	Rouen
France	CHRU de Nancy Brabois	Vandoeuvre les Nancy

Sponsors (4)

Lead Sponsor	Collaborator
Lymphoma Study Association	Eli Lilly and Company, Hoffmann-La Roche, Sanofi-Synthelabo

Country where clinical trial is conducted

France, 

References & Publications (5)

Chau I, Webb A, Cunningham D, Hill M, Rao S, Ageli S, Norman A, Gill K, Howard A, Catovsky D. An oxaliplatin-based chemotherapy in patients with relapsed or refractory intermediate and high-grade non-Hodgkin's lymphoma. Br J Haematol. 2001 Dec;115(4):786-92. — View Citation

Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. — View Citation

Faivre S, Raymond E, Woynarowski JM, Cvitkovic E. Supraadditive effect of 2',2'-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol. 1999;44(2):117-23. — View Citation

Machover D, Delmas-Marsalet B, Misra SC, Gumus Y, Goldschmidt E, Schilf A, Frénoy N, Emile JF, Debuire B, Guettier C, Farrokhi P, Boulefdaoui B, Norol F, Parquet N, Ulusakarya A, Jasmin C. Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma. Ann Oncol. 2001 Oct;12(10):1439-43. — View Citation

Savage DG, Rule SA, Tighe M, Garrett TJ, Oster MW, Lee RT, Ruiz J, Heitjan D, Keohan ML, Flamm M, Johnson SA. Gemcitabine for relapsed or resistant lymphoma. Ann Oncol. 2000 May;11(5):595-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR) (complete response, [CR]; unconfirmed complete response, [CRu] and partial response, [PR])	4 cycles of R-GEMOX	8 weeks	No
Secondary	Overall response rate (ORR) (complete response, [CR]; unconfirmed complete response, [CRu] and partial response, [PR])	completion of the treatment	16 weeks	No
Secondary	Event free survival (EFS)		2 years	No

External Links

•   Official site of the Groupe d'Etudes des Lymphomes de l'Adulte (In french)