Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Gemcitabine

Bendamustine Hydrochloride

Rituximab

Nivolumab

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

Immune Checkpoint Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

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

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

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

70 mg/m2 by intravenous (IV) infusion for up to 2 cycles

Bendamustine hydrochloride

500 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles

Gemcitabine 500 mg

700 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles

Gemcitabine 700 mg

1000 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles

Gemcitabine 1000 mg

1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles

375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles

Boris V Afanasyev, Ph.D

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.

There will be 2 parts in this study. In Part 1, the safety of combination treatment will be evaluated prior to expansion of enrollment to evaluate treatment effect in Part 2. The arms in Part 1 include 3 different dosage regimens of gemcitabine (500 / 700 / 1000). Part 2 of the study will further characterize the safety and evaluate the antitumor activity of drug combination by enrolling patients at the recommended dose schedule determined in Part 1.

Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL

A Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab Combination (BeGeRN) in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

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), 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.

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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL	NCT03259529	Diffuse Large B...	Bendamustine hy... Gemcitabine 500... Gemcitabine 700... Gemcitabine 100... Nivolumab Rituximab	18 Years - 70 Years	St. Petersburg State Pavlov Medical University
Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL	NCT03259529	Diffuse Large B...	Bendamustine hy... Gemcitabine 500... Gemcitabine 700... Gemcitabine 100... Nivolumab Rituximab	18 Years - 70 Years	St. Petersburg State Pavlov Medical University
Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL	NCT03259529	Diffuse Large B...	Bendamustine hy... Gemcitabine 500... Gemcitabine 700... Gemcitabine 100... Nivolumab Rituximab	18 Years - 70 Years	St. Petersburg State Pavlov Medical University

Spots Global Cancer Trial Database for gemcitabine 500 mg