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Diffuse Large B-Cell LymphomaPhase 1/2NCT06249191

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 Phase 1/2 study testing Biopsy, Biospecimen Collection and Bone Marrow Aspiration and Biopsy in people with Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma, run by OHSU Knight Cancer Institute at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Biopsy, Biospecimen Collection and Bone Marrow Aspiration and Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
13 Jun 2024to 1 Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 [SHL]), 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 (patients with measurable disease prior to the pre-phase who have disappearance of measurable disease at initiation of study therapy cycle 1 day 1 [C1D1] are eligible)
  • Confirmed availability of archival or freshly collected tumor tissue before study enrollment
Show all 13Show fewer
  • 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 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 (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

Who cannot join

  • Pregnant or breast /chestfeeding
  • Prior treatment for DLBCL. Exceptions:
  • Course of bendamustine plus rituximab (BR) treatment > 3 years prior for follicular lymphoma, or any history of rituximab treatment
  • As a pre-phase therapy, the following are allowed:
  • Prednisone of ≤ 100 mg for up to a total of 14 days. Prednisone or equivalent corticosteroid must be discontinued by the time of treatment start. These days do NOT have to be consecutive (i.e., can include multiple courses as long as ≤ 14 days)
  • One cycle of RCHOP (can be dose reduced) or DA R EPOCH or BR or single agent rituximab
Show all 50Show fewer
  • Radiation to up to 3 disease sites
  • For chemotherapy and radiation, a washout of 3 weeks is required (exception: for mediastinal/pericardial radiation, the washout is 4 weeks)
  • 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).
  • History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Exceptions:
  • Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement may be eligible.
  • Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Participants with a history of disease-related immune thrombocytopenic purpura, autoimmune hemolytic anemia, or other stable autoimmune diseases may be eligible after review and approval by the primary investigator (PI)
  • Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of pre-phase treatment with prednisone up to 100 mg daily for 7 days (or equivalent corticosteroid dose) prior to cycle 1 day 1 (C1D1). Exceptions:
  • The use of inhaled corticosteroids is permitted.
  • The use of mineralocorticoids for management of orthostatic hypotension is permitted.
  • The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted
  • Known active central nervous system (CNS) involvement of lymphoma
  • Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease. Exceptions:
  • Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator are allowed.
  • Participants with a history of epilepsy who have had no seizures in the past 2 years while not receiving any anti-epileptic medications are allowed in the expansion cohorts only
  • Prior radiotherapy to the mediastinal / pericardial region within 4 weeks
  • Prior pre-phase chemotherapy and radiation, within 3 weeks is required (Exception noted for mediastinal/pericardial radiation)
  • Malignancy treated with curative intent unless in documented remission without treatment for 2 years prior to enrollment, or other malignancy that could affect compliance with the protocol or interpretation of results. Exception: Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer is permitted
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the Participant, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
  • Significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
  • Significant cardiovascular disease, defined as
  • New York Heart Association [NYHA] Class III or IV cardiac disease,
  • Congestive heart failure,
  • Myocardial infarction within the previous 6 months,
  • Unstable arrhythmias, or
  • Unstable angina
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) 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 10 days before C1D1
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 2.5 x ULN
  • Total bilirubin ≥ 1.5 x ULN
  • International normalization ratio (INR) > 1.5 x ULN in the absence of therapeutic anticoagulation
  • Partial prothrombin time (PTT) or adjusted partial prothrombin time (aPTT) > 1.5 x ULN in the absence of a lupus anticoagulant
  • Herbal therapies intended as treatment of lymphoma
  • Medicinal or recreational cannabis products are not permitted while receiving the study intervention.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

    Stephen E. Spurgeon, 503-494-0174, spurgeos@ohsu.edu

    Stephen E. Spurgeon

    Recruiting

Other trials in United States

About this study

Official title: A Phase Ib/II Study Evaluating the Safety and Efficacy of DA EPOCH in Combination With Mosuntuzumab (EPICSUN) in Previously Untreated C-Myc Rearrangement Positive High-Grade B Cell Lymphomas Including Myc Rearranged Diffuse Large B Cell Lymphoma and High Grade B Cell Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of the mosunetuzumab (M) plus dose-adjusted (DA) etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone [EPOCH] combination in previously untreated c-Myc + diffuse large B cell lymphoma (DLBCL) and high-grade B cell lymphoma. (Phase Ib) II. Evaluate the efficacy of M DA EPOCH as complete response (CR) in previously untreated c-Myc + DLBCL and high grade B cell lymphoma. (Phase II)

SECONDARY OBJECTIVES:

  1. Evaluate the efficacy of M DA EPOCH in Phase Ib and II as overall response, durability of response, and survival.

II. Ongoing evaluation of the toxicity and tolerability of M DA EPOCH. (Phase Ib and II) III. Summarize DA EPOCH treatment details when received as part of M DA EPOCH. (Phase Ib and II)

EXPLORATORY OBJECTIVES:

  1. Assess utilization and benefit of tocilizumab for toxicity management. (Phase Ib and II) II. Assess toxicity of M DA EPOCH based on immune related AEs (irAEs). (Phase Ib and II) III. Identify baseline factors of response and progression. (Phase Ib and II) IV. Assess the immune response to mosunetuzumab in the setting of the M DA EPOCH regimen. (Phase Ib and II)

OUTLINE:

Patients receive mosunetuzumab intravenously (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 orally (PO) twice per day (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 multigated acquisition scan (MUGA) at screening and positron emission tomography (PET) scan, computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for 3 years.

Being tested
Biopsy, Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Computed Tomography, Cyclophosphamide
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tumor biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518

    Given IV

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo echocardiography

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • MosunetuzumabBiological

    Also called Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT 4465A, BTCT-4465A, BTCT4465A

    Given IV

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET scan

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • VincristineDrug

    Also called LCR, Leurocristine, VCR, Vincrystine

    Given IV

Study groups in NCT06249191
Study groupRoleWhat they receive
Treatment (Mosunetuzumab and EPOCH)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 reporting using with the American Society for Transplantation and Cellular Therapy (ASTCT) grading system. Safe dose of mosunetuzumab (or dose adjusted [DA] etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone [EOPCH]) will be specified.

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

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

    Will be reported with exact 95% confidence interval.

    Measured: Up to 5 years

Secondary outcomes (6)

  1. Overall response rate (ORR) by PET-CT

    ORR defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) among all efficacy evaluable participants by the EOT disease assessment. Will be reported with exact 95% confidence interval, by mosunetuzumab dose level if applicable.

    Measured: Up to 5 years

  2. Duration of response (DOR)

    Descriptive statistics such as median DOR, with minimum and maximum DOR, will be reported by mosunetuzumab dose level if applicable.

    Measured: 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

  3. Progression free survival (PFS)

    Are estimated in the efficacy set using the Kaplan Meier method. We will report median PFS and corresponding 95% confidence interval for participants by mosunetuzumab dose level if applicable.

    Measured: 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

  4. Overall survival (OS)

    Are estimated in the efficacy set using the Kaplan Meier method. We will report median OS and corresponding 95% confidence interval for participants by mosunetuzumab dose level if applicable.

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

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

    Per ASTCT for CRS and ICANS;CTCAE v5.0 otherwise

    Measured: Up to to 30 days after last dose of mosunetuzumab

  6. Number of cycles completed and dose received of DA EPOCH

    Measured: Up to to 30 days after last dose of DA EPOCH

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2024
  2. Study start13 Jun 2024
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06249191
Sponsor's protocol ID
STUDY00023707
Other IDs
NCI-2024-00070, STUDY00023707
Status last verified
Jul 2026
First submitted
31 Jan 2024
Last updated
7 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biopsy, Biospecimen Collection and Bone Marrow Aspiration and Biopsy in people with Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 50 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities (DLTs) (phase Ib) (time frame: From the first dose of mosunetuzumab to the end of cycle 2 (1 cycle = 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06249191.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.

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