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

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
Russian Federation
Study Type
Interventional
Intervention
Bendamustine hydrochloride
Gemcitabine 500 mg
Gemcitabine 700 mg
Gemcitabine 1000 mg
Nivolumab
Rituximab
Sponsored by
St. Petersburg State Pavlov Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring Diffuse Large B-cell Lymphoma, Nivolumab, Bendamustine Hydrochloride, Gemcitabine, Rituximab

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Sites / Locations

  • First Pavlov State Medical University of St. Petersburg

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Gemcitabine 500

Gemcitabine 700

Gemcitabine 1000

Arm Description

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

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03
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)
Progression-Free Survival (PFS)
Overall Survival (OS)

Full Information

First Posted
August 22, 2017
Last Updated
June 2, 2021
Sponsor
St. Petersburg State Pavlov Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03259529
Brief Title
Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL
Acronym
BeGeRN
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
March 27, 2017 (Actual)
Primary Completion Date
January 27, 2020 (Actual)
Study Completion Date
January 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Petersburg State Pavlov Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
Diffuse Large B-cell Lymphoma, Nivolumab, Bendamustine Hydrochloride, Gemcitabine, Rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gemcitabine 500
Arm Type
Experimental
Arm Description
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
Arm Title
Gemcitabine 700
Arm Type
Experimental
Arm Description
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
Arm Title
Gemcitabine 1000
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Bendamustine hydrochloride
Other Intervention Name(s)
Ribomustin
Intervention Description
70 mg/m2 by intravenous (IV) infusion for up to 2 cycles
Intervention Type
Drug
Intervention Name(s)
Gemcitabine 500 mg
Other Intervention Name(s)
Gemzar
Intervention Description
500 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Intervention Type
Drug
Intervention Name(s)
Gemcitabine 700 mg
Other Intervention Name(s)
Gemzar
Intervention Description
700 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Intervention Type
Drug
Intervention Name(s)
Gemcitabine 1000 mg
Other Intervention Name(s)
Gemzar
Intervention Description
1000 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles
Primary Outcome Measure Information:
Title
The recommended phase 2 dose (RP2D)
Description
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
Time Frame
6 months
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03
Description
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).
Time Frame
12 months
Title
Duration of Response (DOR)
Time Frame
12 months
Title
Progression-Free Survival (PFS)
Time Frame
12 months
Title
Overall Survival (OS)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boris V Afanasyev, Ph.D
Organizational Affiliation
St. Petersburg State Pavlov Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
First Pavlov State Medical University of St. Petersburg
City
Saint-Petersburg
ZIP/Postal Code
197089
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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