An Open-Label, Single Center Phase 2 Study of Magrolimab, Rituximab and Radiation as Bridging Strategy Before CAR T-Cell Therapy in Patients With Relapsed or Refractory Large B-cell Lymphoma

NCT05929716 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-1011NCI-2023-05051
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the efficacy of the combination of magrolimab, rituximab, and radiation as bridging therapy in patients with relapsed or refractory LBCL who receive CAR T-Cell Therapy (CART).

Conditions

Large B-cell Lymphoma; B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (1)

magrolimab, rituximab, and radiation, CAR T leukapheresis

EXPERIMENTAL

Participants may receive radiation therapy at any time during the study. Participants will be given Magrolimab by vein once weekly for 4 doses by vein on an outpatient basis over about 180 minutes starting on Day 1 of Cycle 1. Participants will be given Rituximab by vein once weekly for 4 doses over about 3-4 hours starting on Day 1 of Cycle 1. You will be given rituximab about 30 minutes (no more than 90 minutes) after magrolimab therapy finishes. Participants will receive 1 dose of magrolimab and rituximab by vein one week before your CAR T leukapheresis and then 3 weekly doses of each drug starting 1 day after leukapheresis that will complete 1 week before lymphodepleting chemotherapy for CAR T

Drug: Magrolimab; Drug: Rituximab; Drug: CAR T leukapheresis; Drug: Radiation

Interventions

Magrolimab DRUG

Given by IV (vein)

magrolimab, rituximab, and radiation, CAR T leukapheresis

Rituximab DRUG

Given by IV (vein)

magrolimab, rituximab, and radiation, CAR T leukapheresis

CAR T leukapheresis DRUG

Given by IV (vein)

magrolimab, rituximab, and radiation, CAR T leukapheresis

Radiation DRUG

Given by IV (vein)

magrolimab, rituximab, and radiation, CAR T leukapheresis

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory DLBCL, PMBCL, tFL, or HGBCL, at least 1 prior line of systemic therapy
• Planned to receive standard of care therapy with axi-cel, tisa-cel or liso-cel
• ≥ 18 years of age because no dosing or adverse event data are currently available on the use of magrolimab in combination with rituximab and radiation in patients \<18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Measurable nodal disease of ≥ 1.5 cm, extra-nodal disease \> 1 cm, or splenomegaly \> 12 cm, deemed appropriate for radiation
• At least two weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic immune checkpoint inhibitory/immune stimulatory therapy. At least 3 half-lives must have elapsed from any prior systemic immune checkpoint inhibitory/immune stimulatory therapy at the time the subject is planned for leukapheresis
• Toxicities due to prior systemic and local therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)
• Absolute neutrophil count of ≥ 1.0×109/L, with no G-CSF support for 1 week
• Platelet count of ≥ 50×109/L and hemoglobin \> 9 g/dL without transfusion for 7 days prior to screening assessment
• Creatinine clearance (as estimated by Cockcroft Gault) ≥ 30 mL/min
• Serum alanine transaminase (ALT) / aspartate transaminase (AST) ≤ 2.5 upper limit of normal (ULN)
• Total bilirubin ≤1.5 mg/dL, except in subjects with Gilbert's syndrome.
• Cardiac ejection fraction ≥ 45% with no evidence of clinically significant pericardial effusion
• Baseline oxygen saturation \> 92% on room air
• No evidence of active lymphoma involving the central nervous system (CNS) at time of screening per investigator clinical assessment

You may not qualify if:

• Subjects will be ineligible for this study if they meet the following criteria:
• History of malignancy other than nonmelanoma skin cancer or localized carcinoma (e.g. cervix, bladder, breast, prostate) unless disease free for at least 3 years.
• History of Richter's transformation of chronic lymphocytic leukemia (CLL)
• Autologous stem cell transplantation within 6 weeks of planned CART infusion
• History of allogeneic stem cell transplantation within 12 weeks of planned CART infusion
• Has any condition that requires systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 28 days prior to first dose of study drug (inhaled or topical; corticosteroids; pre-medication for treatment; short course not to exceed 5 days; or brief course of steroids given for prophylaxis of contrast dye allergic response are permitted).
• Known presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Principal investigator.
• Known history of infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of HIV, hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing. For subjects with a history of Hepatitis B or C, standard of care monitoring for viral reactivation will be conducted. Subjects with a history of Hepatitis B will be required to undergo hepatitis B reactivation prophylaxis unless contraindicated.
• Subjects with known detectable cerebrospinal fluid malignant cells or known active brain malignant lesions
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
• History of primary immunodeficiency
• History of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last year considered significant in the opinion of the principal investigator
• History of symptomatic deep vein thrombosis or symptomatic pulmonary embolism within 6 months of enrolment considered significant in the opinion of the principal investigator
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment in the investigator's opinion
• Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

magrolimab; Rituximab; Radiation

Condition Hierarchy (Ancestors)

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Physical Phenomena

Study Officials

• Paolo Strati, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: July 3, 2023
• Study Start: September 30, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: November 13, 2023

Record last verified: 2023-11