This is a phase II multicenter, open-label study of polatuzumab vedotin administered by IV infusion in combination with standard doses of bendamustine (B) and rituximab (R) in transplant-eligible patients with relapsed or refractory DLBCL. A total of 22 patients will be enrolled over a period of 2 years through the University of Colorado and additional study sites if applicable. Study treatment will be given in 21-day cycles for patients with DLBCL.
The first day of treatment will constitute Cycle 1 Day 1. Patients will be treated with a minimum of three cycles and up to a maximum of 6 cycles to optimize responses prior to ASCT based on investigator discretion. All patients will be evaluated for safety and efficacy according to the schedules of assessments. All patients will be assessed for response to treatment by the investigator with the use of standard criteria according to the Modified Lugano Response Criteria at the following time points: * At the time of screening * At the time of primary response assessment (3 weeks after completion of study treatment (i.e., 3 weeks after Cycle 3 Day 1 or after last dose of study medication) Imaging at these timepoints must include FDG-PET (18F-fluorodeoxyglucose-positron emission tomography) and a diagnostic-quality CT scan with both oral and IV contrast. A combined PET/CT scan is encouraged if feasible. CT scans with oral and IV contrast should include neck, chest, abdomen, and pelvic scans. In patients for whom contrast is contraindicated, (e.g., patients with contrast allergy or impaired renal clearance or patient denial), PET-CT scans without contrast are permitted so long as they permit consistent and precise measurement of target lesions during the study treatment period. Patients will also be evaluated every 3 months for 2 years, or until disease progression, death, withdrawal of consent, or initiation of another anti-cancer therapy. Tumor assessments should also be performed to confirm clinical suspicion of relapse or disease progression for documentation. The study will end when all patients enrolled have been followed until death, have withdrawn consent, have been lost to follow-up, until 2-year follow up, or the Sponsor-investigator decides to end the trial, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Polatuzumab vedotin is an ADC designed for the targeted delivery of MMAE(mono-methyl auristatin E), a potent microtubule inhibitor to lymphoma cells expressing CD79b. MMAE has a mechanism of action that is similar to that of vincristine.
Complete response at primary response
The assessment is based on PET/CT, as determined by the investigator
Time frame: 3 weeks after last dose of study medication
objective response at primary response
assessment based on PET/CT as determined by the investigator
Time frame: 3 weeks after last dose of study medication
duration of response (DOR) of combination therapy
DOR, defined as the time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause based on PET/CT or CT only as determined by the investigator assessment.Response assessment will be determined according to Modified Lugano Response Criteria for Malignant Lymphoma (Lugano Classification)
Time frame: 2 years of follow up
number of patients who underwent an ASCT
Determined during follow up
Time frame: 2 years of follow up
Cell of Origin analysis
Cell of origin analysis will be based on immunohistochemistry analysis
Time frame: 2 years of follow up
Differences in response rates based on timing of relapse
\<12 months of front-line R-chemotherapy versus \>12 months after front-line R-chemotherapy and bulky disease prior to ASCT (bulk defined as mass \> 7.5 cms)
Time frame: 2 years of follow up
c-Myc status
by FISH
Time frame: 2 years of follow up
2-yr progression free survival (PFS)
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PFS, defined as the time from date of first treatment to the first occurrence of progression or relapse, or death from any cause, based on PET/CT or CT only as determined by the investigator assessment
Time frame: 2 years of follow up
overall survival (OS)
defined as the time from the date of randomization or first treatment to the date of death from any cause
Time frame: 2 years of follow up
stem cell collection failure rate
Stem cells will be collected post primary response assessment. If patients achieve a PR after 3 cycles of Pola+BR and investigator decides to give additional cycles of Pola+BR (up to a max of 6 cycles) then stem cell collection may occur between cycles to minimize the chances of collection failure.
Time frame: 2 years of follow up