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

NCT03259529 | Completed Phase 1

• 1 other identifier: DLBCL BeGeRN 1/2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Diffuse Large B-cell Lymphoma; Nivolumab; Bendamustine Hydrochloride; Gemcitabine; Rituximab

Outcome Measures

Primary Outcomes (2)

• The recommended phase 2 dose (RP2D)

  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

  6 months

• Overall Response Rate (ORR)

  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.

  12 months

Secondary Outcomes (4)

• Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03

  12 months

• Duration of Response (DOR)

  12 months

• Progression-Free Survival (PFS)

  12 months

• Overall Survival (OS)

  12 months

Study Arms (3)

Gemcitabine 500

EXPERIMENTAL

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; Drug: Gemcitabine 500 mg; Drug: Nivolumab; Drug: Rituximab

Gemcitabine 700

EXPERIMENTAL

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; Drug: Gemcitabine 700 mg; Drug: Nivolumab; Drug: Rituximab

Gemcitabine 1000

EXPERIMENTAL

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; Drug: Gemcitabine 1000 mg; Drug: Nivolumab; Drug: Rituximab

Interventions

Bendamustine hydrochloride DRUG

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

Also known as: Ribomustin

Gemcitabine 1000; Gemcitabine 500; Gemcitabine 700

Gemcitabine 500 mg DRUG

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

Also known as: Gemzar

Gemcitabine 500

Gemcitabine 700 mg DRUG

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

Also known as: Gemzar

Gemcitabine 700

Gemcitabine 1000 mg DRUG

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

Also known as: Gemzar

Gemcitabine 1000

Nivolumab DRUG

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

Also known as: Opdivo

Gemcitabine 1000; Gemcitabine 500; Gemcitabine 700

Rituximab DRUG

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

Gemcitabine 1000; Gemcitabine 500; Gemcitabine 700

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

First Pavlov State Medical University of St. Petersburg

Saint Petersburg, 197089, Russia

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Bendamustine Hydrochloride; Gemcitabine; Nivolumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Study Officials

• Boris V Afanasyev, Ph.D

  St. Petersburg State Pavlov Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation

Model Details: 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.

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 23, 2017
• Study Start: March 27, 2017
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: June 7, 2021

Record last verified: 2021-06

Locations

RU (1)