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CyBeR Association in Relapsed/Refractory DLBCL (CyBeR-Lymph)

Primary Purpose

Diffuse Large B Cell Lymphoma

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Rituximab

Bendamustine

Cytarabine

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
- Carcinoma in situ of the breast.
- Incidental histological finding of prostate cancer (TNM stage of T1a or T1b).
renal impairment with an estimated (modified dietin renal disease; MDRD) creatinine clearance < 40 ml/min,
chronic liver disease or day-1 (AST/ALT )≥2.5 upper limit of normal (ULN), total bilirubin≥1.5 ULN,

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DLBCL patients

Arm Description

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

Outcomes

Primary Outcome Measures

treatment response

established with 1999 Cheson criteria on CT-scan

Secondary Outcome Measures

overall survival

progression free survival

Full Information

NCT ID

NCT02758925

First Posted

April 14, 2016

Last Updated

May 3, 2016

Sponsor

University Hospital, Caen

1. Study Identification

Unique Protocol Identification Number

NCT02758925

Brief Title

CyBeR Association in Relapsed/Refractory DLBCL

Acronym

CyBeR-Lymph

Official Title

Phase 2 Study of Cytarabine in Association With Bendamustine and Rituximab in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Unknown status

Study Start Date

June 2016 (undefined)

Primary Completion Date

November 2018 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Caen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Participants will received 6 cycles every 21 days with a follow-up period of 24 months. CT-Scan after 3 cycles and at the end of the treatment will be used to assess treatment response, established with Cheson criteria in 1999. Principal objective is to obtain an overall response rate of 60% (corresponding to an increased of 15% of the rituximab-gemcitabine-oxaliplatine regimen's overall response rate). Secondaries objectives are to value toxicity, progression free survival and overall survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B Cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

DLBCL patients

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

mabthera

Intervention Description

375mg/m2 IV day 1

Intervention Type

Drug

Intervention Name(s)

Bendamustine

Other Intervention Name(s)

levact

Intervention Description

90mg/m2 IV day 1-2

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Other Intervention Name(s)

aracytine

Intervention Description

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

Primary Outcome Measure Information:

Title

treatment response

Description

established with 1999 Cheson criteria on CT-scan

Time Frame

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

Secondary Outcome Measure Information:

Title

overall survival

Time Frame

2 years

Title

progression free survival

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. Carcinoma in situ of the breast. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b). renal impairment with an estimated (modified dietin renal disease; MDRD) creatinine clearance < 40 ml/min, chronic liver disease or day-1 (AST/ALT )≥2.5 upper limit of normal (ULN), total bilirubin≥1.5 ULN,

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emilie Reboursiere, MD

Phone

+33231272140

reboursiere-e@chu-caen.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gandhi Damaj, PHD

Organizational Affiliation

University Hospital, Caen

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23650408

Citation

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.

Results Reference

background

PubMed Identifier

22530665

Citation

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.

Results Reference

background

PubMed Identifier

23955074

Citation

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.

Results Reference

background

PubMed Identifier

23450436

Citation

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.

Results Reference

background

PubMed Identifier

23401442

Citation

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.

Results Reference

background

PubMed Identifier

23753028

Citation

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.

Results Reference

result

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CyBeR Association in Relapsed/Refractory DLBCL

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