Clinical trial NCT03259529: Safety and Efficacy of Bendamustine, Gemcitabine, Rituximab, Nivolumab (BeGeRN) in Patients With r/r DLBCL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: Diffuse Large B-cell Lymphoma
Nivolumab
Bendamustine Hydrochloride
Gemcitabine
Rituximab
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2017-08-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: The recommended phase 2 dose (RP2D)
timeFrame: 6 months
measure: Overall Response Rate (ORR)
timeFrame: 12 months
Secondary outcomes:
measure: Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03
timeFrame: 12 months
measure: Duration of Response (DOR)
timeFrame: 12 months
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Saint-Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St. Petersburg
Study officials:
affiliation: St. Petersburg State Pavlov Medical University
name: Boris V Afanasyev, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: