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CompletedNCT03259529BeGeRNUpdated Jun 7, 2021

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

A Phase 1/2 interventional study of Bendamustine hydrochloride and Gemcitabine 500 mg in Diffuse Large B Cell Lymphoma, sponsored by St. Petersburg State Pavlov Medical University. Completed at 1 site in Russian Federation. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-06-07.

Sponsored by St. Petersburg State Pavlov Medical University · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Diffuse Large B Cell Lymphoma

Keywords

  • Diffuse Large B-cell Lymphoma
  • Nivolumab
  • Bendamustine Hydrochloride
  • Gemcitabine
  • Rituximab
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
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

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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • 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 · Drug: Gemcitabine 500 mg · Drug: Nivolumab · Drug: Rituximab

  • 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 · Drug: Gemcitabine 700 mg · Drug: Nivolumab · Drug: Rituximab

  • 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 · Drug: Gemcitabine 1000 mg · Drug: Nivolumab · Drug: Rituximab

Interventions

  • DrugBendamustine hydrochloride

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

    Also known as: Ribomustin

  • DrugGemcitabine 500 mg

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

    Also known as: Gemzar

  • DrugGemcitabine 700 mg

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

    Also known as: Gemzar

  • DrugGemcitabine 1000 mg

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

    Also known as: Gemzar

  • DrugNivolumab

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

    Also known as: Opdivo

  • DrugRituximab

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

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 6 months

  2. 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.

    Time frame: 12 months

Secondary outcomes

  1. 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).

    Time frame: 12 months

  2. Duration of Response (DOR)

    Time frame: 12 months

  3. Progression-Free Survival (PFS)

    Time frame: 12 months

  4. Overall Survival (OS)

    Time frame: 12 months

06

Study locations

1 site
  • First Pavlov State Medical University of St. Petersburg
    Saint-Petersburg, 197089, Russian Federation
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03259529
Lead sponsor
St. Petersburg State Pavlov Medical University
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) — Principal investigator
First posted
Aug 23, 2017
Start date
Mar 27, 2017
Primary completion
Jan 27, 2020
Completion
Jan 27, 2020
Last update
Jun 7, 2021

Study contacts

Boris V Afanasyev, Ph.D
principal investigator · St. Petersburg State Pavlov Medical University

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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