Polatuzumab Vedotin With R-GDP in Relapsed/Refractory Diffuse Large B-cell Lymphoma

Trial Title: Polatuzumab Vedotin With R-GDP in Relapsed/Refractory Diffuse Large B-cell Lymphoma

NCT ID: NCT05498220

Condition: Diffuse Large B-cell Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Dexamethasone
Rituximab
Gemcitabine
Polatuzumab vedotin

Conditions: Keywords:
Relapsed
refractory
polatuzumab vedotin
rituximab
gemcitabine
cisplatin

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

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

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Polatuzumab vedotin (PV)
Description: 1.8 mg/kg, intravenous, at day 1, in every 21 days
Arm group label: Single Arm

Intervention type: Drug
Intervention name: Rituximab
Description: 375 mg/m2 intravenous, at day 1 or day 2, in every 21 days
Arm group label: Single Arm

Intervention type: Drug
Intervention name: Hyaluronidase
Description: 1,400 mg/23,400 units sub-cutaneous, starts at cycle 2, in every 21 days
Arm group label: Single Arm

Intervention type: Drug
Intervention name: Gemcitabine
Description: 1,000 mg/m2 intravenous at day 1 and 8, in every 21 days
Arm group label: Single Arm

Intervention type: Drug
Intervention name: Cisplatin
Description: 75 mg/m2, intravenous, at day 1, in every 21 days
Arm group label: Single Arm

Intervention type: Drug
Intervention name: Dexamethasone
Description: 40 mg intravenous at day 1, Per oral days at days 2-4
Arm group label: Single Arm

Intervention type: Drug
Intervention name: GCSF
Description: granulocyte-colony stimulating factor (GCSF )
Arm group label: Single Arm

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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Lineberger Comprehensive Cancer Center

Address:
City: Chapel Hill
Zip: 27514
Country: United States

Status: Recruiting

Contact:
Last name: Lori Stravers

Phone: 919-966-4432
Email: lori_stravers@med.unc.edu

Investigator:
Last name: Christopher Dittus, DO, MPH
Email: Principal Investigator

Start date: February 17, 2023

Completion date: August 2028

Lead sponsor:
Agency: UNC Lineberger Comprehensive Cancer Center
Agency class: Other

Collaborator:
Agency: Genentech, Inc.
Agency class: Industry

Source: UNC Lineberger Comprehensive Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05498220
http://unclineberger.org/patientcare/clinical-trials/clinical-trials