Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Gemcitabine 500 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 |
Drug: Bendamustine hydrochloride
70 mg/m2 by intravenous (IV) infusion for up to 2 cycles
Other Names:
Drug: Gemcitabine 500 mg
500 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Other Names:
Drug: Nivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Other Names:
Drug: Rituximab
375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles
|
Experimental: Gemcitabine 700 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 |
Drug: Bendamustine hydrochloride
70 mg/m2 by intravenous (IV) infusion for up to 2 cycles
Other Names:
Drug: Gemcitabine 700 mg
700 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Other Names:
Drug: Nivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Other Names:
Drug: Rituximab
375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles
|
Experimental: Gemcitabine 1000 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 |
Drug: Bendamustine hydrochloride
70 mg/m2 by intravenous (IV) infusion for up to 2 cycles
Other Names:
Drug: Gemcitabine 1000 mg
1000 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Other Names:
Drug: Nivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Other Names:
Drug: Rituximab
375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles
|
Outcome Measures
Primary Outcome Measures
- 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
- 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).
- Duration of Response (DOR) [12 months]
- Progression-Free Survival (PFS) [12 months]
- Overall Survival (OS) [12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis: Histologically confirmed diffuse large B-cell lymphoma
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Refractory or relapsed after at least two prior lines of treatment (i.e. induction and salvage regimen) for diffuse large B-cell lymphoma.
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Age 18-70 years old
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Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
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Signed informed consent
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No severe concurrent illness
Exclusion Criteria:
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Uncontrolled bacterial or fungal infection at the time of enrollment
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Requirement for vasopressor support at the time of enrollment
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Karnofsky index <30%
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Pregnancy
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Somatic or psychiatric disorder making the patient unable to sign informed consent
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Active or prior documented autoimmune disease requiring systemic treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | First Pavlov State Medical University of St. Petersburg | Saint-Petersburg | Russian Federation | 197089 |
Sponsors and Collaborators
- St. Petersburg State Pavlov Medical University
Investigators
- Principal Investigator: Boris V Afanasyev, Ph.D, St. Petersburg State Pavlov Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DLBCL BeGeRN 1/2