CyBeR Association in Relapsed/Refractory DLBCL

NCT02758925 | Unknown Phase 2 DMC

• 1 other identifier: 2015-005837-37
• Study Type: interventional
• Target: 78
• Locations: 0 countries
• Sites: N/A

Brief Summary

Forty percent of patients with diffuse large B cell lymphoma (DLBCL) have primary refractory or relapsed disease (R/R). For these fit patients, standard treatment in second line therapy is high dose therapy with autologous stem cell transplantation (ASCT). In 48% of DLBCL no ASCT is possible due to progressive disease. For these patients or ineligible to transplantation patients, salvage therapy is often rituximab-gemcitabine-oxaliplatine regimen with an overall response rate (ORR) about 50%. Bendamustine in combination with rituximab, used as a single agent in the setting of R/R DLBCL patients, have shown an ORR of 62.7% and 45.8% with a good safety profile. Bendamustine and cytarabine (BAC) showed high synergy in inducing cell death in mantle cell lymphoma and DLBCL cell lines. In a recent phase II study, the combination of cytarabine with Rituximab and Bendamustine (R-BAC) in patients with mantle cell lymphoma who were previously untreated, refractory or relapsed was evaluated. The efficacy and safety of the R-BAC association will be evaluated in this phase II trial enrolling 78 patients with relapsed or refractory DLBCL.

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• treatment response

  established with 1999 Cheson criteria on CT-scan

  up to 20 weeks (at the end of the treatment)

Secondary Outcomes (2)

• overall survival

  2 years

• progression free survival

  2 years

Study Arms (1)

DLBCL patients

EXPERIMENTAL

they will receive a combination of: Rituximab 375mg/m2 IV at Day 1 Bendamustine 90mg/m2 IV at Day 1 and 2 Cytarabine 1000mg/m2 IV at day 2 every 21 days for 6 cycles

Drug: Rituximab; Drug: Bendamustine; Drug: Cytarabine

Interventions

Rituximab DRUG

375mg/m2 IV day 1

Also known as: mabthera

DLBCL patients

Bendamustine DRUG

90mg/m2 IV day 1-2

Also known as: levact

DLBCL patients

Cytarabine DRUG

1000mg/m2 or 750mg/m2 at day 2 if patients aged more than 70 years or toxicity grade 3/4

Also known as: aracytine

DLBCL patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients from 18 to 75 years
• Patient sharpened the social security system
• Patients with relapsed or refractory diffuse large B cell lymphoma who received at least one prior line of immunochemotherapy unfit for intensive regimen therapy and autologous stem cell transplantation (ASCT) eligible patients to stem cell transplantation with failure of the salvage therapy patients with relapse after ASCT
• Not previously treated with bendamustine
• WHO performance status 0, 1 or 2
• Adequate hematological function as defined by: leucocyte count ≥ 3.0 109/L, platelet count ≥ 75 109/L
• Females of childbearing potential must agree to have a medically acceptable method of contraception from study treatment initiation until the end of treatment.
• Signed informed consent.

You may not qualify if:

• Person under guardianship or curatorship , or unable to understand the purpose of the study
• Central nervous system or meningeal involvement
• WHO performance status more than 2
• Contraindication to any drug contained in the chemotherapy regimen
• HIV disease, active hepatitis B or C
• Any serious active disease or co-morbid medical condition
• Any of the following laboratory abnormalities.
• Leucocyte count \< 3.0 x 109/L
• Platelet count \< 75 x 109/L
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or lactating females.
• Prior history of malignancies, other than lymphoma, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
• Basal cell carcinoma of the skin.
• Squamous cell carcinoma of the skin.
• Carcinoma in situ of the cervix.

Sponsors & Collaborators

• University Hospital, Caen: lead

Related Publications (6)

• Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. doi: 10.1200/JCO.2012.46.5203. Epub 2013 May 6.

  PMID: 23650408 BACKGROUND

• Castegnaro S, Visco C, Chieregato K, Bernardi M, Albiero E, Zanon C, Madeo D, Rodeghiero F. Cytosine arabinoside potentiates the apoptotic effect of bendamustine on several B- and T-cell leukemia/lymphoma cells and cell lines. Leuk Lymphoma. 2012 Nov;53(11):2262-8. doi: 10.3109/10428194.2012.688200. Epub 2012 May 21.

  PMID: 22530665 BACKGROUND

• Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. doi: 10.1007/s00277-013-1879-x. Epub 2013 Aug 17.

  PMID: 23955074 BACKGROUND

• Visco C, Finotto S, Pomponi F, Sartori R, Laveder F, Trentin L, Paolini R, Di Bona E, Ruggeri M, Rodeghiero F. The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia. Am J Hematol. 2013 Apr;88(4):289-93. doi: 10.1002/ajh.23391. Epub 2013 Feb 28.

  PMID: 23450436 BACKGROUND

• Visco C, Finotto S, Zambello R, Paolini R, Menin A, Zanotti R, Zaja F, Semenzato G, Pizzolo G, D'Amore ES, Rodeghiero F. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 2013 Apr 10;31(11):1442-9. doi: 10.1200/JCO.2012.45.9842. Epub 2013 Feb 11.

  PMID: 23401442 BACKGROUND

• Mounier N, El Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. doi: 10.3324/haematol.2013.090597. Epub 2013 Jun 10.

  PMID: 23753028 RESULT

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Bendamustine Hydrochloride; Cytarabine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gandhi Damaj, PHD

  University Hospital, Caen

  STUDY DIRECTOR

Central Study Contacts

Emilie Reboursiere, MD

CONTACT

+33231272140; reboursiere-e@chu-caen.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: May 3, 2016
• Study Start: June 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: December 1, 2018
• Last Updated: May 4, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share