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

Diffuse Large B Cell Lymphoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03259529
• Other study ID #: DLBCL BeGeRN 1/2
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 27, 2017
• Est. completion date: January 27, 2020

Study information

• Verified date: June 2021
• Source: St. Petersburg State Pavlov Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 27, 2020
• Est. primary completion date: January 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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

Locations

Country	Name	City	State
Russian Federation	First Pavlov State Medical University of St. Petersburg	Saint-Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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).	12 months
Secondary	Duration of Response (DOR)		12 months
Secondary	Progression-Free Survival (PFS)		12 months
Secondary	Overall Survival (OS)		12 months