Diffuse Large B Cell Lymphoma
Conditions
Keywords
Diffuse Large B-cell Lymphoma, Nivolumab, Bendamustine Hydrochloride, Gemcitabine, Rituximab
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.
Interventions
DRUGBendamustine hydrochloride
70 mg/m2 by intravenous (IV) infusion for up to 2 cycles
DRUGGemcitabine 500 mg
500 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
DRUGGemcitabine 700 mg
700 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
1000 mg/m2 by intravenous (IV) infusion on day 1,8,15 for up to 2 cycles
DRUGNivolumab
1 mg/kg by intravenous (IV) infusion on day 1,15 for up to 2 cycles
DRUGRituximab
375 mg/m2 by intravenous (IV) infusion on day 0 for up to 2 cycles
Sponsors
St. Petersburg State Pavlov Medical University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The recommended phase 2 dose (RP2D) | 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 |
| Overall Response Rate (ORR) | 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
| Measure | Time frame | Description |
|---|---|---|
| Frequency of grade 3 or higher treatment-related adverse events by CTCAE 4.03 | 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). |
| Duration of Response (DOR) | 12 months | — |
| Progression-Free Survival (PFS) | 12 months | — |
| Overall Survival (OS) | 12 months | — |
Countries
Russia
Outcome results
None listed