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

St. Petersburg State Pavlov Medical University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Diffuse Large B Cell Lymphoma

Treatments: Drug: Gemcitabine 500 mg; Drug: Gemcitabine 700 mg; Drug: Gemcitabine 1000 mg; Drug: Rituximab; Drug: Bendamustine hydrochloride; Drug: Nivolumab

Study type: Interventional

Funder types: Other

Identifiers

NCT03259529

DLBCL BeGeRN 1/2

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Gemcitabine 500

Experimental group

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

Treatment:

Drug: Nivolumab

Drug: Bendamustine hydrochloride

Drug: Rituximab

Drug: Gemcitabine 500 mg

Gemcitabine 700

Experimental group

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

Treatment:

Drug: Nivolumab

Drug: Bendamustine hydrochloride

Drug: Rituximab

Drug: Gemcitabine 700 mg

Gemcitabine 1000

Experimental group

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

Treatment:

Drug: Nivolumab

Drug: Bendamustine hydrochloride

Drug: Gemcitabine 1000 mg

Drug: Rituximab