Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
A Phase 1 Study of Mosunetuzumab With Polatuzumab Vedotin and Lenalidomide (M+Pola+Len) in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
4 other identifiers
interventional
30
1 country
8
Brief Summary
This phase I trial studies the side effects and best dose of mosunetuzumab when given together with polatuzumab vedotin and lenalidomide in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mosunetuzumab and polatuzumab vedotin are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Polatuzumab, linked to a toxic agent called vedotin, attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Lenalidomide may stimulate or suppress the immune system in different ways and stop cancer cells from growing and by preventing the growth of new blood vessels that cancer cells need to grow. Giving mosunetuzumab with polatuzumab vedotin and lenalidomide may work better in treating patients with relapsed/refractory DLBCL.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2024
Typical duration for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2023
CompletedFirst Posted
Study publicly available on registry
August 29, 2023
CompletedStudy Start
First participant enrolled
May 20, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
April 30, 2026
April 1, 2026
3.1 years
August 26, 2023
April 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Safety and tolerability of monsunetuzumab+polatuzumab vedotin+lenalidomide for determination of recommended phase 2 dose
Dose limiting toxicity will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
During cycle 1 (cycle=28 days)
Secondary Outcomes (4)
Objective response rate
Up to 2 years
Complete response rate
Up to 2 years
Progression free survival
Up to 2 years
Duration of response
From time of initial response assessment demonstrating at least partial response until disease response assessment that demonstrates progressive disease, assessed up to 2 years
Other Outcomes (9)
CD79b expression levels
At baseline
Frequency of CD4 T-cells and IFN-gamma+ producing CD4 T-cells
At baseline and up to 2 years
Ultrasensitive determination of cytokine profile
At baseline and up to 2 years
- +6 more other outcomes
Study Arms (1)
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
EXPERIMENTALPatients receive mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Cycles repeat every 28 days for 8 cycles in patients who achieve a CR or up to 17 cycles for patients with a PR or SD in the absence of disease progression or unacceptable toxicity. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles of polatuzumab vedotin repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Cycles of lenalidomide repeat every 28 days for 8 cycles in patients who achieve CR, or up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Undergo PET/CT
Given PO
Given IV
Given IV
Undergo PET/CT
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed DLBCL NOS, high-grade B-cell lymphoma, or transformed indolent lymphoma as per the World Health Organization 2022 criteria
- All patients will have relapsed/refractory DLBCL after 1 or more prior lines of therapy with the exception of patients receiving CAR T in second line that have a D score of 3 at day (D)+ 30 through D+ 90
- Patients who progressed/relapsed after prior polatuzumab vedotin are allowed
- For the expansion cohorts only: cohort A must have Deauville score of ≥ 3 with the first 90 days) after standard of care chimeric antigen receptor (CAR) T-cell therapy; cohort B- other patients with relapsed/refractory after 1 or more prior lines of therapy (e.g. relapse after Day 90 from CAR-T, or relapsed after other therapies and were not considered candidates for CAR-T)
- All patients that have failed 1 line of therapy will be eligible with the exception of a 12 patient cohort (A) that will require prior CAR T therapy
- Measurable disease by CT or PET scan, with one or more sites of disease \>= 1.5 cm in longest dimension
- Age \>= 18 years
- Because no dosing or adverse event data are currently available on the use of mosunetuzumab in combination with polatuzumab vedotin, and lenalidomide in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy \>= 12 weeks
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 50,000/mcL without transfusion for 2 weeks prior to cycle 1 day 1 (C1D1)
- Hemoglobin \>= 9 g/dL
- Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 × ULN may be enrolled)
- Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 × ULN (AST and/or ALT =\< 5 × ULN for patients with liver involvement)
- +15 more criteria
You may not qualify if:
- Plasmablastic lymphoma, primary mediastinal B-cell lymphoma, gray zone lymphoma
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents or treatments
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to mosunetuzumab or other agents used in study
- Patients with uncontrolled intercurrent illness
- Uncontrolled or known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to first study treatment administration
- Active CNS involvement or detectable disease by lymphoma, including leptomeningeal involvement
- Pregnant women are excluded from this study because mosunetuzumab is bispecific antibody with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with mosunetuzumab, breastfeeding should be discontinued if the mother is treated with mosunetuzumab. These potential risks may also apply to other agents used in this study. Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab, 3 months after the final dose of polatuzumab vedotin, and 1 month after the final dose of lenalidomide
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2 or better
- Known or suspected chronic active Epstein-Barr virus (EBV) infection
- Patients with any other significant condition(s) that would make this protocol unreasonably hazardous
- Current \> grade 1 peripheral neuropathy
- Prior solid organ transplantation
- Patients with known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Northwestern University
Chicago, Illinois, 60611, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Joseph M Tuscano
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 26, 2023
First Posted
August 29, 2023
Study Start
May 20, 2024
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
April 30, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.