Trial Title:
Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
NCT ID:
NCT06015880
Condition:
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
High Grade B-Cell Lymphoma
Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lenalidomide
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Immunoconjugates
Polatuzumab vedotin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Given PO
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
Other name:
CC 5013
Other name:
CC-5013
Other name:
CC5013
Other name:
CDC 501
Other name:
Revlimid
Intervention type:
Biological
Intervention name:
Mosunetuzumab
Description:
Given IV
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
Other name:
Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A
Other name:
BTCT 4465A
Other name:
BTCT-4465A
Other name:
BTCT4465A
Other name:
CD20/CD3 BiMAb BTCT4465A
Other name:
Lunsumio
Other name:
Mosunetuzumab-axgb
Other name:
RG 7828
Other name:
RG-7828
Other name:
RG7828
Other name:
RO7030816
Intervention type:
Drug
Intervention name:
Polatuzumab Vedotin
Description:
Given IV
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
Other name:
ADC DCDS4501A
Other name:
Antibody-Drug Conjugate DCDS4501A
Other name:
DCDS4501A
Other name:
FCU 2711
Other name:
FCU-2711
Other name:
FCU2711
Other name:
polatuzumab vedotin-piiq
Other name:
Polivy
Other name:
RG 7596
Other name:
RG-7596
Other name:
RG7596
Other name:
Ro 5541077-000
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of mosunetuzumab + polatuzumab vedotin +
lenalidomide in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL).
SECONDARY OBJECTIVE:
I. To observe and record anti-tumor activity of the combination of mosunetuzumab,
polatuzumab vedotin, and lenalidomide in R/R DLBCL.
EXPLORATORY OBJECTIVES:
I. To assess the efficacy in patients that have failed prior polatuzumab vedotin
containing regimens (i.e., patients who progressed/relapsed after prior polatuzumab).
II. To assess anti-tumor activity in patients that a) have < complete response (CR) or
Deauville score of 3 or worse at day 90 (D90) (or before) after standard of care chimeric
antigen receptor (CAR) T-cell therapy; b) other patients who have failed prior treatment
(e.g. relapse after day 90 from CAR-T, or relapsed after other therapies and were not
considered candidates for CAR-T).
III. To identify biomarkers that can predict the response to mosunetuzumab + polatuzumab
vedotin + lenalidomide.
IV. To describe anti-tumor activity in patients whose tumors have previously failed to
respond to polatuzumab (i.e., patients who progressed/relapsed after prior polatuzumab).
OUTLINE: This is a dose-escalation study of mosunetuzumab, followed by a dose-expansion
study.
Patients receive mosunetuzumab intravenously (IV) over 2-4 hours on days 1, 8, and 15 of
cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8
cycles in patients who achieve a complete response (CR) or up to 17 cycles for patients
with a partial response (PR) or stable disease (SD) in the absence of disease progression
or unacceptable toxicity. Patients also receive polatuzumab vedotin IV over 30-90 minutes
on day 1 for 6 cycles and lenalidomide orally (PO) on days 1-21 for 8 cycles in patients
who achieve CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease
progression or unacceptable toxicity. Patients undergo positron emission tomography
(PET)/ computed tomography (CT) and blood sample collection throughout the study.
After completion of study treatment, patients are followed up for 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 < complete response (CR) or
Deauville score of 3 or 4 at D90 (or before) 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 or
autologous hematopoietic cell transplantation)
- 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)
- Alkaline phosphatase 2.5 × ULN (=< 5 × ULN for patients with documented liver
involvement or bone metastases)
- Creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault: (140- age) × (weight
in kg) × (0.85 if female) 72 × (serum creatinine in mg/dL)
- International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) =< 1.5 × ULN (This applies only to patients who do not receive therapeutic
anticoagulation; patients receiving therapeutic anticoagulation, such as
low-molecular-weight heparin or warfarin, should be on a stable dose.)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging 6-8
weeks after central nervous system (CNS)-directed therapy shows no evidence of
progression or CNS lymphoma
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, and agreement to refrain
from donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of
1% per year during the treatment period and for 3 months after the final dose
of mosunetuzumab, 3 months after the final dose of polatuzumab vedotin, and 1
month after the last dose of lenalidomide
- For men: agreement to remain abstinent (refrain from heterosexual intercourse)
or use a condom, and agreement to refrain from donating sperm, as defined
below:
- With female partners of childbearing potential, men must remain abstinent or
use a condom during the treatment period, 5 months after the final dose of
polatuzumab vedotin, and 1 month after the last dose of lenalidomide
- Some concurrent cancer therapeutics (e.g., prostate, breast hormonal-based therapy)
are allowed
- Ability to understand and the willingness to sign a written informed consent
document. Legally authorized representatives may sign and give informed consent on
behalf of study participants
- Agree to comply with all local requirements of the lenalidomide risk minimization
plan
Exclusion Criteria:
- 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 2B 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)
- Patients with history of confirmed progressive multifocal leukoencephalopathy
(PML)
- Currently active or uncontrolled autoimmune disease
- Patients with a history of autoimmune-related hypothyroidism on a stable
dose of thyroid replacement hormone may be eligible
- Patients with controlled type 1 diabetes mellitus who are on an insulin
regimen are eligible for the study
- Patients with a history of disease-related immune thrombocytopenic
purpura, autoimmune hemolytic anemia, or other stable autoimmune diseases
may be eligible
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center LAO
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joseph M. Tuscano
Email:
joseph.tuscano@ucdmc.ucdavis.edu
Investigator:
Last name:
Joseph M. Tuscano
Email:
Principal Investigator
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-826-4673
Email:
becomingapatient@coh.org
Investigator:
Last name:
Geoffrey Shouse
Email:
Principal Investigator
Facility:
Name:
University of California Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
916-734-3089
Investigator:
Last name:
Joseph M. Tuscano
Email:
Principal Investigator
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
312-695-1301
Email:
cancer@northwestern.edu
Investigator:
Last name:
Reem Karmali
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Sami Ibrahimi
Email:
Principal Investigator
Facility:
Name:
University of Virginia Cancer Center
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
434-243-6303
Email:
uvacancertrials@hscmail.mcc.virginia.edu
Investigator:
Last name:
Emily Ayers
Email:
Principal Investigator
Start date:
May 20, 2024
Completion date:
June 29, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06015880
