Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma

NCT06594939 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00056497
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm, interventional phase 2 study is designed to evaluate whether the inclusion of mosunetuzumab subcutaneous and polatuzumab vedotin (Mosun-Pola) to a split-dose CHP chemotherapy backbone will improve outcomes for elderly patients with a new diagnosis of diffuse large B-cell lymphoma.

Conditions

Diffuse Large B Cell Lymphoma (DLBCL)

Keywords

Mosunetuzumab; Polatuzumab vedotin

Outcome Measures

Primary Outcomes (1)

• Complete Response

  This is defined as the number of subjects achieving a complete response at the end of treatment using the Lugano criteria.

  Up to six months.

Secondary Outcomes (10)

• Partial Response

  Up to six months

• Duration of Response

  Up to 60 months

• Overall Survival

  2 years

• Adverse Events

  Up to 7 months

• Study therapy completion

  Up to 6 months

Study Arms (1)

Mosum-Pola-SD-CHP

EXPERIMENTAL

Each cycle is 28 days and consists of one "A" treatment on Day 1 and one "B" treatment on Day 15 for six cycles. Day 1 ("A" part of cycle) Polatuzumab Vedotin 1.8 mg/kg Intravenous (IV); Mosunetuzumab (Cycle 1A) 5 mg Subcutaneous (SC); Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 2 ("A" part of cycle) Pegfilgrastim 6 mg SC Day 8 ("A" part of cycle) Mosunetuzumab 45 mg SC Day 15 ("B" part of cycle) Mosunetuzumab (Cycle 1B-6B) 45 mg SC; Cyclophosphamide 375 mg/m\^2 IV; Doxorubicin 25 mg/m\^2 IV; Prednisone 50 mg Orally Day 16 ("B" part of cycle) Pegfilgrastim 6 mg SC

Drug: Polatuzumab Vedotin; Drug: Mosunetuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Other: Pegfilgrastim

Interventions

Doxorubicin DRUG

Chemotherapy drug, anthracycline antibiotic.

Also known as: Adriamycin

Mosum-Pola-SD-CHP

Prednisone DRUG

Steroid, anti-inflammatory

Mosum-Pola-SD-CHP

Polatuzumab Vedotin DRUG

A combination of a monoclonal antibody and a chemotherapy drug.

Also known as: Polivy

Mosum-Pola-SD-CHP

Mosunetuzumab DRUG

A monoclonal antibody.

Also known as: Lunsumio

Mosum-Pola-SD-CHP

Cyclophosphamide DRUG

Chemotherapy drug, alkylating agent.

Also known as: Cytoxan

Mosum-Pola-SD-CHP

Pegfilgrastim OTHER

Granulocyte stimulating factor, biologic response modifier.

Also known as: filgrastim

Mosum-Pola-SD-CHP

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients aged 70-74 who are determined to be unfit or frail by the Cumulative Illness Rating Scale-Geriatric (CIRS-G) score with 5-8 comorbid conditions scored 2 or more than 1 comorbidity scored 3-4 are allowed.
• Newly diagnosed, untreated, biopsy-proven CD20 positive diffuse large B-cell lymphoma (DLBCL) (including high-grade B-cell lymphoma and T-cell/histiocyte-rich large B-cell lymphoma). Patients with discordant bone marrow (i.e., involved by low-grade/indolent non-Hodgkin lymphoma) are eligible. Patients with transformed DLBCL from underlying low-grade disease are eligible. Patients with composite DLBCL and concurrent low-grade lymphoma are eligible. Patients with prior treatment for low-grade NHL with non-anthracycline based regimens are eligible.
• a. Short-course prednisone or equivalent steroid for symptom management is allowable for up to seven days.
• Measurable disease by positron emission tomography (PET) / computed tomography (CT) using the Lugano criteria (lymph node \>1.5 cm or extranodal site \>1.0 cm).
• Adequate biospecimen sample that meets current Adaptive Clonality ID Test specimen requirements for DLBCL.
• a. Note: the preferred ID specimen type is a formalin-fixed paraffin-embedded (FFPE) lymph node biopsy, either FFPE slides or scrolls, targeting 40 microns of material.
• Left ventricular ejection fraction ≥50% by echocardiography or multigated acquisition (MUGA) scan.
• Karnofsky Performance Score ≥50 or Eastern Cooperative Oncology Group (ECOG) scan 0-2.
• Ann Arbor Stage II bulky, III, or IV disease.
• Minimum life expectancy greater than 3 months (should be explicitly documented by the enrolling investigator).
• Negative HIV test. Individuals with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥200/µL, and have an undetectable viral load, and have not had a history of opportunistic infection attributable to acquired immunodeficiency syndrome (AIDS) within the last 12 months.
• For patients with hepatitis B virus antigen (HBsAg) or core antibody (HBcAb) seropositivity, patients must have a negative hepatitis B viral load and an appropriate prophylaxis plan must be in place during chemotherapy therapy treatment. For all patients that are hepatitis B core antibody positive, they should take entecavir prophylaxis (0.5 mg by mouth daily) until 1 year from completion of chemotherapy. Hepatitis B viral load should be checked on these patients prior to starting chemotherapy and every 3 months thereafter if initial hepatitis B viral load is negative (±1 week if chemotherapy cycle is delayed). If hepatitis B viral load is positive, hepatology or ID referral is recommended, and hepatitis B viral load should be checked monthly and every 3 months for 12 months after end of treatment.
• For patients with hepatitis C Ab positivity, a viral load must be checked and negative for enrollment.
• Negative SARS-CoV-2 antigen or polymerase chain reaction (PCR) test within 7 days prior to enrollment.
• Had at least one dose of a COVID-19 vaccine approved or authorized for emergency use by the FDA.

You may not qualify if:

• Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy.
• Current Grade \>1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease.
• Prior allogeneic or autologous stem cell transplant.
• Prior solid organ transplant.
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
• Known or suspected chronic active Epstein-Barr Virus (EBV) infection.
• History of progressive multifocal leukoencephalopathy (PML).
• Current or within 6 months of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
• Patients with SARS-CoV-2 antigen or PCR testing positivity within 30 days prior to Cycle 1 Day 1.
• a. Any patient with documented SARS-CoV-2 infection within 6 months prior to planned Cycle 1 Day 1 must have no persistent respiratory symptoms, no evidence of residual sequelae, and have a negative PCR test for SARS-CoV-2.
• Administration of a live, attenuated vaccine within 4 weeks before start of study therapy or anticipation that such a live, attenuated vaccine will be required during the study.
• On immunosuppressant therapy for an active autoimmune disease, including, but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• a. Exceptions may be made for patients with a remote history of or well-controlled autoimmune disease, excluding patients on systemic immunosuppression for autoimmune disease, or patients who received such immunosuppression within 1 year prior.
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
• Recent major surgery within 4 weeks before the start of C1D1 with the exception of lymph node biopsies for diagnosis.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

polatuzumab vedotin; Cyclophosphamide; Doxorubicin; Prednisone; pegfilgrastim; Filgrastim

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)

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; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Nirav Shah, MD

  Medical College of Wisconsin

  STUDY CHAIR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)