Mosunetuzumab With Chemotherapy for the Treatment of Patients With Untreated C-Myc Rearrangement Positive High Grade B Cell Lymphoma or Diffuse Large B Cell Lymphoma

NCT06249191 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: STUDY00023707NCI-2024-00070
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II clinical trial tests the safety, side effects, and effectiveness of mosunetuzumab with chemotherapy for the treatment of patients with untreated, c-Myc rearrangement positive, high grade B cell lymphoma or diffuse large B cell lymphoma. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as mosunetuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone work in different ways to stop the growth of cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mosunetuzumab with chemotherapy may be safe, tolerable and/or effective in treating patients with untreated, c-Myc rearrangement positive, high grade B cell lymphoma or diffuse large B cell lymphoma.

Conditions

Diffuse Large B-Cell Lymphoma; High Grade B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs) (phase Ib)

  Using a modified 3+3 design in previously untreated c-Myc rearranged aggressive B cell lymphomas during the safety run-in period (cycle 1-2). Incidence of DLTs will be tabulated by dose level. All DLTs will be coded by system organ class, MedDRA preferred term, and severity grade using Common Terminology Criteria for Adverse Events (CTCAE )(version \[v\] 5.0). Cytokine Release Syndrome/Immune Effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) toxicities will be graded with the American Society for Transplantation and Cellular Therapy (ASTCT) system. Safe dose of mosunetuzumab (or dose adjusted \[DA\] etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone \[EOPCH\]) will be specified.

  From the first dose of mosunetuzumab to the end of cycle 2 (1 cycle = 21 days)

• Proportion of patients with complete response by positron emission tomography-computed tomography (PET-CT) (phase II)

  Will be reported with exact 95% confidence interval.

  Up to 5 years

Secondary Outcomes (6)

• Overall response rate (ORR) by PET-CT

  Up to 5 years

• Duration of response (DOR)

  From first documented evidence of documented CR or PR to first occurrence of disease progression as determined by the investigator, or death from any cause, whichever occurs first, assessed up to 5 years

• Progression free survival (PFS)

  From the first dose of mosunetuzumab to first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first, assessed up to 5 years

• Overall survival (OS)

  From first dose of mosunetuzumab to death by any cause, assessed up to 5 years

• Incidence of ≥ grade 3 toxicities possibly or definitely related to mosunetuzumab

  Up to to 30 days after last dose of mosunetuzumab

Study Arms (1)

Treatment (Mosunetuzumab and EPOCH)

EXPERIMENTAL

Patients receive mosunetuzumab IV, over 2-4 hours, on day 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients receive etoposide IV, doxorubicin IV, and vincristine IV on days 1-4, cyclophosphamide IV, over 2 hours, on day 5 and prednisone PO BID on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity for up to 6 cycles. Patients undergo bone marrow aspiration and biopsy, tumor biopsy and may undergo echocardiography or MUGA at screening and PET scan, CT scan or MRI and blood sample collection throughout the study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Doxorubicin; Procedure: Echocardiography; Drug: Etoposide; Procedure: Magnetic Resonance Imaging; Biological: Mosunetuzumab; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Drug: Prednisone; Drug: Vincristine

Interventions

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (Mosunetuzumab and EPOCH)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Mosunetuzumab and EPOCH)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (Mosunetuzumab and EPOCH)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (Mosunetuzumab and EPOCH)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, WR-138719

Treatment (Mosunetuzumab and EPOCH)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (Mosunetuzumab and EPOCH)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (Mosunetuzumab and EPOCH)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP16

Treatment (Mosunetuzumab and EPOCH)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (Mosunetuzumab and EPOCH)

Mosunetuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT 4465A, BTCT-4465A, BTCT4465A, CD20/CD3 BiMAb BTCT4465A, Lunsumio, Mosunetuzumab-axgb, RG 7828, RG-7828, RG7828, RO7030816

Treatment (Mosunetuzumab and EPOCH)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (Mosunetuzumab and EPOCH)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (Mosunetuzumab and EPOCH)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (Mosunetuzumab and EPOCH)

Vincristine DRUG

Given IV

Also known as: LCR, Leurocristine, VCR, Vincrystine

Treatment (Mosunetuzumab and EPOCH)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For both phases of the study, participant must be 18-75 years of age and have previously untreated high-grade B cell lymphoma (HGBCL) or diffuse large B cell lymphoma (DLBCL), including transformed DLBCL per the World Health Organization (WHO) 2022 classification, and with documented c-Myc rearrangement on fluorescence in situ hybridization (FISH) testing. Eligible types of c-Myc rearrangements will be performed by FISH testing and may include any single MYC rearrangement (single-hit lymphoma), Double hit (DHL) lymphoma or and triple hit (THL) lymphoma defined by translocations of MYC and BCL2 (DHL) and BCL6 (THL)
• Pathology must be verified and confirmed by university pathologists at the enrolling institution and centrally (OHSU) for any biopsies read outside of either institution
• Stage II or higher and International Prognostic Index (IPI) score of 2-5
• Able to comply with the study protocol and procedures, in the investigator's judgment
• At least one bi-dimensionally measurable nodal lesion, defined as ≥ 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as ≥ 1.0 cm in its longest diameter
• Confirmed availability of archival or freshly collected tumor tissue before study enrollment
• Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
• Left ventricular ejection fraction (LVEF) defined by multiple-gated acquisition (MUGA) scan or echocardiogram (ECHO) within the institutional limits of normal
• Absolute neutrophil count (ANC) ≥ 1.0 ×10\^9/L (14 days prior to first mosunetuzumab dose) (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement, or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) without transfusion
• Platelet count ≥ 75 ×10\^9/L (14 days prior to first mosunetuzumab dose) (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement, or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) without transfusion
• Total hemoglobin ≥ 10 g/dL (21 days prior to first mosunetuzumab dose) (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement, or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) without transfusion
• Serum creatinine ≤ upper limit of normal (ULN); or estimated creatinine clearance ≥ 50 mL/min by Cockcroft Gault method or other institutional standard methods, e.g. based on nuclear medicine renal scan
• For persons of childbearing potential (PCBP), an agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year, and confirmed agreement to refrain from donating eggs, during the treatment period and for at least 3 months after the last dose of mosunetuzumab, and 3 months after the last dose of tocilizumab (if applicable), whichever is longer
• For participants who can produce sperm and create pregnancy: confirmed agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

You may not qualify if:

• Pregnant or breast /chestfeeding
• Prior treatment for DLBCL. Exceptions:
• Prednisone of ≤ 100 mg for up to 10 days, within 28 days prior to starting study treatment. Prednisone or equivalent corticosteroid must be discontinued by the time of treatment start
• One cycle of RCHOP or DA R EPOCH
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Contraindication to receive full dose of any of the individual components of EPOCH
• Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Known or suspected chronic active Epstein Barr virus (CAEBV) infection
• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology)
• \* Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening. These Participants must be willing to undergo monthly DNA testing and appropriate antiviral therapy as indicated
• Acute or chronic hepatitis C virus (HCV) infection. Participants positive for HCV by antibody testing, but negative for HCV by polymerase chain reaction (PCR) are eligible
• HIV seropositivity
• Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
• Prior solid organ transplantation
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Genentech, Inc.: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Biopsy; Specimen Handling; Cyclophosphamide; Doxorubicin; Etoposide; Magnetic Resonance Spectroscopy; Prednisone; deltacortene; prednylidene; Vincristine

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Spectrum Analysis; Chemistry Techniques, Analytical; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Stephen E Spurgeon

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 8, 2024
• Study Start: June 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)