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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Polatuzumab vedotin (PV); Drug: Rituximab; Drug: Hyaluronidase; Drug: Gemcitabine; Drug: Cisplatin; Drug: Dexamethasone; Drug: GCSF

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lori Stravers; Phone Number: 919-966-4432; Email: Lori_Stravers@med.unc.edu
• Study Contact Backup: Name: Leah Randolph; Phone Number: 919-966-4432; Email: Leah_Randolph@med.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • Lineberger Comprehensive Cancer Center
      • Principal Investigator: Christopher Dittus, DO, MPH
      • Contact: Lori Stravers; Phone Number: 919-966-4432; Email: Lori_Stravers@med.unc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm; The subjects with diffuse large B-cell lymphoma were relapsed or refractory after the first treatment and receiving the study protocol treatment.

Drug: Polatuzumab vedotin (PV); 1.8 mg/kg, intravenous, at day 1, in every 21 days; Drug: Rituximab; 375 mg/m2 intravenous, at day 1 or day 2, in every 21 days; Drug: Hyaluronidase; 1,400 mg/23,400 units sub-cutaneous, starts at cycle 2, in every 21 days; Drug: Gemcitabine; 1,000 mg/m2 intravenous at day 1 and 8, in every 21 days; Drug: Cisplatin; 75 mg/m2, intravenous, at day 1, in every 21 days; Drug: Dexamethasone; 40 mg intravenous at day 1, Per oral days at days 2-4; Drug: GCSF; granulocyte-colony stimulating factor (GCSF )

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR is defined as the proportion of subjects who received the study treatment, and achieved complete response (CR) or partial response (PR) by Lugano classification. Complete Response: Complete metabolic response on Positron emission tomography (PET) image or Target nodes/nodal masses must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease on Computerized Tomography (CT). Partial Response: Score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size on PET and ≥50% decrease in the sum of the products of diameters (SPD) of up to 6 target measurable nodes and extranodal sites on CT.	Up to 4 months (End of Treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CR)	CR is defined as the proportion of subjects who received the study treatment, achieved complete response (CR) by the Lugano classification.	Up to 4 months (End of Treatment)
Progression free survival (PFS)	PFS is defined as the time from the start of study treatment until progression by Lugano classification or death. Progressive Disease: Score 4 or 5 with an increase in the intensity of uptake from baseline and/or new fluorodeoxyglucose (FDG) -avid foci consistent with lymphoma at the interim or end-of-treatment assessment on PET, or an individual node/lesion must be abnormal with LDi > 1.5 cm, increase by ≥ 50% from the cross product of the shortest axis perpendicular to LDi (SDi) nadir and an increase in LDi or SDi from nadir: 0.5 cm for lesions ≤ 2 cm, 1.0 cm for lesions > 2 cm.	Up to 2 years
Overall Survival (OS)	OS is defined as the time from the start of treatment until death from any cause.	Up to 2 years
Number of participants with adverse events	The number of participants with adverse events will be listed and tabulated by grade to determine the safety and toxicity. Adverse Events will be graded according to The National Cancer Institute (NCI) of Common Terminology Criteria for Adverse Events (CTCAE) version 5. The scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.	Up to 2 years

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Christopher Dittus, DO, MPH, Division of Hematology | Lymphoma Program Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cisplatin; Relapsed; rituximab; gemcitabine; refractory; polatuzumab vedotin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Immunoconjugates; Dexamethasone; Rituximab; Gemcitabine; Polatuzumab vedotin
• Other Study ID Numbers: LCCC2033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No