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

NCT05498220 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC2033
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Relapsed; refractory; polatuzumab vedotin; rituximab; gemcitabine; cisplatin

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the number 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 Outcomes (5)

• Complete Response Rate (CR)

  Up to 4 months (End of Treatment)

• Progression Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

• Number of Participants With Adverse Events

  Up to 2 years

• Number of Participants With Serious Adverse Events

  Up to 2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

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); Drug: Rituximab; Drug: Hyaluronidase; Drug: Gemcitabine; Drug: Cisplatin; Drug: Dexamethasone; Drug: GCSF

Interventions

Polatuzumab vedotin (PV) DRUG

1.8 mg/kg, intravenous, at day 1, in every 21 days

Single Arm

Rituximab DRUG

375 mg/m2 intravenous, at day 1 or day 2, in every 21 days

Single Arm

Hyaluronidase DRUG

1,400 mg/23,400 units sub-cutaneous, starts at cycle 2, in every 21 days

Single Arm

Gemcitabine DRUG

1,000 mg/m2 intravenous at day 1 and 8, in every 21 days

Single Arm

Cisplatin DRUG

75 mg/m2, intravenous, at day 1, in every 21 days

Single Arm

Dexamethasone DRUG

40 mg intravenous at day 1, Per oral days at days 2-4

Single Arm

GCSF DRUG

granulocyte-colony stimulating factor (GCSF )

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Radiologic evidence of active disease within 28 days of starting trial therapy.
• Only one prior line of therapy.
• 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.
• Subjects may be eligible or ineligible for autologous stem cell transplant

You may not qualify if:

• 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.
• 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.
• Women who are pregnant or breastfeeding or who intend to become pregnant within a year of the last dose of study treatment.
• 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.
• Previous exposure to polatuzumab vedotin.
• History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine.
• Contraindication to gemcitabine or cisplatin, or dexamethasone or similar corticosteroid.
• Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction \< 40%, symptomatic coronary artery disease or symptomatic arrhythmias.
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation \> 91% on room air.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

polatuzumab vedotin; Rituximab; Hyaluronoglucosaminidase; Gemcitabine; Cisplatin; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

The study was terminated upon reaching its accrual goal; however, the number of enrolled subjects was insufficient to support the planned analysis.

Results Point of Contact

• Title: Melahat Canter
• Organization: UNC Lineberger

Melahat_Canter@med.unc.edu

(919) 962-0000

Study Officials

• Christopher Dittus, DO, MPH

  Division of Hematology | Lymphoma Program Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 9, 2022
• First Posted: August 11, 2022
• Study Start: February 17, 2023
• Primary Completion: March 7, 2025
• Study Completion: October 3, 2025
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)