CyBeR Association in Relapsed/Refractory DLBCL

Phase 2

• Conditions: Diffuse Large B Cell Lymphoma
• Interventions: Drug: Rituximab; Drug: Bendamustine; Drug: Cytarabine

• Registration Number: NCT02758925
• Lead Sponsor: University Hospital, Caen

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.

Study Timeline

• Study First Submitted: 2016-04-14
• Study First Submitted QC: 2016-04-29
• Status Verified: 2016-05
• Study First Posted: 2016-05-03
• Last Update Submitted: 2016-05-03
• Last Update Posted: 2016-05-04
• Study Start: 2016-06
• Primary Completion: 2018-11
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. patients from 18 to 75 years
2. Patient sharpened the social security system
3. 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
4. Not previously treated with bendamustine
5. WHO performance status 0, 1 or 2
6. Adequate hematological function as defined by: leucocyte count ≥ 3.0 109/L, platelet count ≥ 75 109/L
7. Females of childbearing potential must agree to have a medically acceptable method of contraception from study treatment initiation until the end of treatment.
8. Signed informed consent.

Exclusion Criteria

1. Person under guardianship or curatorship , or unable to understand the purpose of the study

2. Central nervous system or meningeal involvement

3. WHO performance status more than 2

4. Contraindication to any drug contained in the chemotherapy regimen

5. HIV disease, active hepatitis B or C

6. Any serious active disease or co-morbid medical condition

7. Any of the following laboratory abnormalities.

   • Leucocyte count < 3.0 x 109/L
   • Platelet count < 75 x 109/L

8. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

9. Pregnant or lactating females.

10. 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).

11. renal impairment with an estimated (modified dietin renal disease; MDRD) creatinine clearance < 40 ml/min,

12. chronic liver disease or day-1 (AST/ALT )≥2.5 upper limit of normal (ULN), total bilirubin≥1.5 ULN,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DLBCL patients	Bendamustine	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
DLBCL patients	Rituximab	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
DLBCL patients	Cytarabine	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

Primary Outcome Measures

Name	Time	Method
treatment response	up to 20 weeks (at the end of the treatment)	established with 1999 Cheson criteria on CT-scan

Secondary Outcome Measures

Name	Time	Method
overall survival	2 years
progression free survival	2 years