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

Sponsor
St. Petersburg State Pavlov Medical University (Other)
Overall Status
Completed
CT.gov ID
NCT03259529
Collaborator
(none)
30
1
3
34
0.9

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

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention 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.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)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 27, 2017
Actual Primary Completion Date :
Jan 27, 2020
Actual Study Completion Date :
Jan 27, 2020

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:
  • Ribomustin
  • Drug: Gemcitabine 500 mg
    500 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
    Other Names:
  • Gemzar
  • Drug: Nivolumab
    1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
    Other Names:
  • Opdivo
  • 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:
  • Ribomustin
  • Drug: Gemcitabine 700 mg
    700 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
    Other Names:
  • Gemzar
  • Drug: Nivolumab
    1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
    Other Names:
  • Opdivo
  • 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:
  • Ribomustin
  • Drug: Gemcitabine 1000 mg
    1000 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
    Other Names:
  • Gemzar
  • Drug: Nivolumab
    1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
    Other Names:
  • Opdivo
  • Drug: Rituximab
    375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    1. 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).

    2. Duration of Response (DOR) [12 months]

    3. Progression-Free Survival (PFS) [12 months]

    4. Overall Survival (OS) [12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    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.
    Responsible Party:
    Ivan S Moiseev, Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, St. Petersburg State Pavlov Medical University
    ClinicalTrials.gov Identifier:
    NCT03259529
    Other Study ID Numbers:
    • DLBCL BeGeRN 1/2
    First Posted:
    Aug 23, 2017
    Last Update Posted:
    Jun 7, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Ivan S Moiseev, Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, St. Petersburg State Pavlov Medical University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 7, 2021