Clinical trial NCT05498220: Polatuzumab Vedotin With R-GDP in Relapsed/Refractory Diffuse Large B-cell Lymphoma
Official title: A Phase II Trial Evaluating the Efficacy of Polatuzumab Vedotin With Rituximab, Gemcitabine, Dexamethasone, and Cisplatin (PV-RGDP) Chemotherapy for Relapsed or Refractory Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Relapsed
refractory
polatuzumab vedotin
rituximab
gemcitabine
cisplatin
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2022-08-11
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study will use a Simon two-stage design. In the first stage 27 evaluable subjects will be recruited. If there are at least 13 (≥ 13) subjects with a partial or complete response after 4 cycles, another 17 subjects will be enrolled and treated in the second stage of the trial, for a total of 44 evaluable subjects.
Primary purpose: TREATMENT

Brief summary: This study aimed to evaluate the efficacy of a novel regimen consisting of polatuzumab vedotin in combination with rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) for the treatment of diffuse large B-cell lymphoma that either came back or did not improve after the treatments (rrDLBCL).

This combination has not been approved by the Food and Drug Administration (FDA) for the treatment of rrDLBCL. Salvage therapy (treatment after standard treatment failed) needs to be improved. Rituximab, gemcitabine, dexamethasone, and cisplatin combination is a standard therapy for rrDLBCL and polatuzumab vedotin (PV) is a novel antibody-drug conjugate targeting CD79b. PV has shown efficacy in the setting of rrDLBCL and can improve the response rates of standard salvage therapy.

This study will focus on subjects in the first relapse (one prior regimen) and will include both subjects who are transplant eligible and those who are transplant ineligible.


Eligibility criteria: In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.

Inclusion Criteria:

1. Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
2. Biopsy proven diffuse large B-cell lymphoma (DLBCL) in the first relapse (biopsy can be from initial diagnosis). The study will allow high-grade B cell lymphoma, but not including Burkitt's lymphoma.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
4. Radiologic evidence of active disease within 28 days of starting trial therapy.
5. Only one prior line of therapy.
6. Prior cancer treatment must be completed at least 14 days prior to the start of treatment and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or start of treatment.
7. Subjects may be eligible or ineligible for autologous stem cell transplant

Exclusion Criteria:

1. Known severe, active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment that may put the subject at undue risk as determined by the investigator.
2. Subjective hearing loss interfering with daily activities or evidence of greater than mild hearing loss compared to age appropriate normal on screening audiometry are excluded.
3. Women who are pregnant or breastfeeding or who intend to become pregnant within a year of the last dose of study treatment.
4. Subjects with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drugs are eligible for enrollment in the trial.
5. Previous exposure to polatuzumab vedotin.
6. History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine.
7. Contraindication to gemcitabine or cisplatin, or dexamethasone or similar corticosteroid.
8. Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction \< 40%, symptomatic coronary artery disease or symptomatic arrhythmias.
9. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation \> 91% on room air.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 4 months (End of Treatment)
Secondary outcomes:
measure: Complete response rate (CR)
timeFrame: Up to 4 months (End of Treatment)
measure: Progression free survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Number of participants with adverse events
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Division of Hematology | Lymphoma Program Lineberger Comprehensive Cancer Center
name: Christopher Dittus, DO, MPH
role: PRINCIPAL_INVESTIGATOR
References: