Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL
- Conditions
- Diffuse Large B Cell Lymphoma
- Interventions
- Registration Number
- NCT03259529
- Lead Sponsor
- St. Petersburg State Pavlov Medical University
- Brief Summary
Despite the current advances in clinical oncology, the prognosis of patients with resistant diffuse large B cell lymphoma or relapse after high dose chemotherapy is dismal. Therefore there is a need for the introduction of novel treatment regimens. This phase I/II trial evaluates the safety and efficacy of combination bendamustine, gemcitabine, nivolumab and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. The safety of combination treatment will be evaluated with the determination of recommended dose schedule prior to expansion of enrollment to evaluate the antitumor activity of bendamustine, gemcitabine, rituximab, and nivolumab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- Diagnosis: Histologically confirmed diffuse large B-cell lymphoma
- Refractory or relapsed after at least two prior lines of treatment (i.e. induction and salvage regimen) for diffuse large B-cell lymphoma.
- Age 18-70 years old
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
- Signed informed consent
- No severe concurrent illness
- Uncontrolled bacterial or fungal infection at the time of enrollment
- Requirement for vasopressor support at the time of enrollment
- Karnofsky index <30%
- Pregnancy
- Somatic or psychiatric disorder making the patient unable to sign informed consent
- Active or prior documented autoimmune disease requiring systemic treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Gemcitabine 500 Nivolumab Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 500 Rituximab Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 1000 Bendamustine hydrochloride Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 500 Gemcitabine 500 mg Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 700 Gemcitabine 700 mg Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 1000 Gemcitabine 1000 mg Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 1000 Nivolumab Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 700 Bendamustine hydrochloride Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 500 Bendamustine hydrochloride Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 500 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 700 Rituximab Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 700 Nivolumab Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 700 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days Gemcitabine 1000 Rituximab Days 1,2 Bendamustine Hydrochloride 70 mg/m2/day iv; Days 1,8,15 Gemcitabine 1000 mg/m2/day iv; Days 1,15 Nivolumab 1mg/kg/day iv; Day 0 Rituximab 375mg/kg/day iv. Duration of cycle 28 days
- Primary Outcome Measures
Name Time Method The recommended phase 2 dose (RP2D) 6 months The recommended phase 2 dose (RP2D) of Bendamustine Hydrochloride and Gemcitabine in combination with Nivolumab and Rituximab in patients with Diffuse Large B-cell Lymphoma
Overall Response Rate (ORR) 12 months Overall response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) in measurable lesions as defined by LYRIC criteria and duration of response.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 12 months Duration of Response (DOR) 12 months Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03 12 months Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).
Progression-Free Survival (PFS) 12 months
Trial Locations
- Locations (1)
First Pavlov State Medical University of St. Petersburg
🇷🇺Saint-Petersburg, Russian Federation
First Pavlov State Medical University of St. Petersburg🇷🇺Saint-Petersburg, Russian Federation