Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03259529
Recruitment Status : Completed
First Posted : August 23, 2017
Last Update Posted : May 28, 2020
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

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
Diffuse Large B Cell Lymphoma Drug: Bendamustine hydrochloride Drug: Gemcitabine 500 mg Drug: Gemcitabine 700 mg Drug: Gemcitabine 1000 mg Drug: Nivolumab Drug: Rituximab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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.
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 : March 27, 2017
Actual Primary Completion Date : January 27, 2020
Actual Study Completion Date : January 27, 2020


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/kg by intravenous (IV) infusion for up to 2 cycles
Other Name: Ribomustin

Drug: Gemcitabine 500 mg
500 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Other Name: Gemzar

Drug: Nivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Other Name: 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/kg by intravenous (IV) infusion for up to 2 cycles
Other Name: Ribomustin

Drug: Gemcitabine 700 mg
700 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Other Name: Gemzar

Drug: Nivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Other Name: 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/kg by intravenous (IV) infusion for up to 2 cycles
Other Name: Ribomustin

Drug: Gemcitabine 1000 mg
1000 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
Other Name: Gemzar

Drug: Nivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
Other Name: Opdivo

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




Primary Outcome Measures :
  1. The recommended phase 2 dose (RP2D) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 12 months ]
  3. Progression-Free Survival (PFS) [ Time Frame: 12 months ]
  4. Overall Survival (OS) [ Time Frame: 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03259529


Locations
Layout table for location information
Russian Federation
First Pavlov State Medical University of St. Petersburg
Saint-Petersburg, Russian Federation, 197089
Sponsors and Collaborators
St. Petersburg State Pavlov Medical University
Investigators
Layout table for investigator information
Principal Investigator: Boris V Afanasyev, Ph.D St. Petersburg State Pavlov Medical University
Layout table for additonal information
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: August 23, 2017    Key Record Dates
Last Update Posted: May 28, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ivan S Moiseev, St. Petersburg State Pavlov Medical University:
Diffuse Large B-cell Lymphoma
Nivolumab
Bendamustine Hydrochloride
Gemcitabine
Rituximab
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Rituximab
Nivolumab
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents