Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy

Phase 1/2 Study to Evaluate the Safety, Feasibility, and Efficacy of FP-1201 (Intravenous Interferon-Beta-1a) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy

This phase I/II trial tests the safety and how well intravenous interferon-beta-1a (FP-1201) works in preventing toxicities after CD19-directed chimeric antigen receptor (CAR) T-cell therapy in patients with B-cell cancers that has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Interferon beta-1a is in a class of medications called immunomodulators. It works by protecting the lining of blood vessels, and preventing brain inflammation. Giving FP-1201 may prevent cytokine release syndrome (CRS) and immune effector cell associated-neurotoxicity syndrome (ICANS) toxicities in patients receiving CD19 CAR T-cell therapy with recurrent or refractory B-cell malignancies.

Study Overview

• Status: Withdrawn
• Conditions: Recurrent Mantle Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent B Acute Lymphoblastic Leukemia; Refractory B Acute Lymphoblastic Leukemia; Refractory Mantle Cell Lymphoma
• Intervention / Treatment: Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Aspiration; Procedure: Biopsy; Procedure: X-Ray Imaging; Procedure: Bone Marrow Biopsy; Procedure: Lumbar Puncture; Biological: Interferon Beta-1A; Procedure: Biospecimen Collection

Detailed Description

OUTLINE: This is a dose-escalation study of FP-1201.

Patients undergo leukapheresis prior to treatment and receive FP-1201 intravenously (IV) for 3 days every 24 hours from day -3 through day -1 or for 5 days every 24 hours from day -5 through day -1 or on day -5, day -3, and day -1. Patients may receive lymphodepletion chemotherapy with either cyclophosphamide IV and fludarabine IV on days -5, -4, -3 followed by axi-cel IV or brexu-cel IV on day 0 or fludarabine IV over 30 minutes on days -4, -3, and -2 and cyclophosphamide IV over 60 minutes on day -2 followed by brexu-cel IV on day 0. Patients undergo x-ray imaging and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT as well as lumbar puncture (LP) for cerebral spinal fluid (CSF) collection and/or bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection on study and during follow-up as well as a tissue biopsy during screening and follow-up.

After completion of study treatment, patients are followed up to 28 days and 90 days, then long-term for up to 15 years.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be 18 years of age or older
• Karnofsky performance status of >= 60%
• Participants eligible for treatment with axi-cel or brexu-cel
• Negative serum pregnancy test within 2 weeks of enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
• Fertile male and female participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of FP-1201
• Ability to understand and provide informed consent

Exclusion Criteria:

• Known hypersensitivity to natural or recombinant interferon beta, albumin or any other component of the formulation
• Estimated creatinine clearance (Cockcroft and Gault) =< 60 mL/min
• Significant proteinuria defined as 2+ or 3+ proteinuria or urinary protein >= 1g/24h
• Severe hepatic dysfunction defined as group C of the National Cancer Institute Organ Dysfunction Working Group hepatic impairment criteria (total bilirubin > 3x upper limit of normal [ULN] with any aspartate aminotransferase [AST] or alanine transaminase [AL]T value), or AST or ALT > 3x ULN, unless due to malignancy or Gilbert's syndrome in the opinion of the principal investigator (PI) or designee
• Participants with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing, as clinically indicated. Those with an forced expiratory volume in the first second (FEV1) of < 50 % of predicted or diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected) < 40% will be excluded

• Significant cardiovascular abnormalities as defined by any one of the following:

  • New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension
  • Uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < 35%
• Uncontrolled serious and active infection
• Corticosteroid use (> 20mg/day of prednisone, or equivalent) within 7 days prior to first FP-1201 administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prevention (interferon beta-1A [FP-1201]); Patients undergo leukapheresis prior to treatment and receive FP-1201 IV for 3 days every 24 hours from day -3 through day -1 or for 5 days every 24 hours from day -5 through day -1 or on day -5, day -3, and day -1. Patients may receive lymphodepletion chemotherapy with either cyclophosphamide IV and fludarabine IV on days -5, -4, -3 followed by axi-cel IV or brexu-cel IV on day 0 or fludarabine IV over 30 minutes on days -4, -3, and -2 and cyclophosphamide IV over 60 minutes on day -2 followed by brexu-cel IV on day 0. Patients undergo x-ray imaging and ECHO or MUGA during screening. Patients also undergo CT or PET/CT as well as LP for CSF collection and/or bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection on study and during follow-up as well as a tissue biopsy during screening and follow-up.

Procedure: Computed Tomography; Undergo CT; Other Names: CAT Scan; Computed Axial Tomography; Computerized axial tomography (procedure); Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan; Radionuclide ventriculography; Procedure: Positron Emission Tomography; Undergo PET/CT; Other Names: Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Medical Imaging; Positron emission tomography (procedure); Pet Scan; Procedure: Bone Marrow Aspiration; Undergo bone marrow aspiration; Procedure: Biopsy; Undergo tissue biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: X-Ray Imaging; Undergo x-ray; Other Names: Conventional X-Ray; Diagnostic Radiology; Radiographic Imaging; Radiography; RG; Static X-Ray; Medical Imaging; Plain film radiographs; Radiographic imaging procedure (procedure); Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy; Procedure: Lumbar Puncture; Undergo LP; Other Names: LP; spinal tap; Biological: Interferon Beta-1A; Given IV; Other Names: Avonex; Rebif; BG9418; Recombinant interferon beta-1a; 145258-61-3; Procedure: Biospecimen Collection; Undergo blood and CSF sample collection; Other Names: Biological Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT) rates	Will be summarized in the DLT evaluable population. Final DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm. The target toxicity rate is 30%.	Within 14 days after the last administration of interferon-beta-1a (FP-1201)
Incidence of adverse events (AEs)	Type, frequency, and severity of AEs according to the National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0.	From the first dose of FP-1201 through day 28 after chimeric antigen receptor (CAR) T-cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine release syndrome (CRS) rates	Will be assessed by any grade and grade >= 3 by American Society for Transplantation and Cellular Therapy (ASTCT) criteria and will be summarized along the two-sided 95% Clopper-Pearson confidence interval (CI) based on the CRS and ICANS analysis set.	From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last
Immune effector cell associated-neurotoxicity syndrome (ICANS) rates	Will be assessed by any grade and grade >= 3 by ASTCT criteria and will be summarized along the two-sided 95% Clopper-Pearson CI based on the CRS and ICANS analysis set.	From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last
Cumulative corticosteroids dose	Will be summarized using descriptive statistics (median, quantiles) based on the CRS and ICANS analysis set.	Within 28 days after CAR T-cell infusion
Overall response rate	Will be assessed by the Lugano criteria for B-non-Hodgkin lymphoma (NHL) participants and National Comprehensive Cancer Network (NCCN) criteria for B- acute lymphoblastic leukemia (ALL) participants Will be summarized along with the two-sided Clopper-Pearson CI based on the anti-tumor response evaluable analysis set.	28 days after CAR T-cell infusion
Complete response rate	Will be assessed by the Lugano criteria for B-NHL participants and NCCN criteria for B-ALL participants Will be summarized along with the two-sided Clopper-Pearson CI based on the anti-tumor response evaluable analysis set.	28 days after CAR T-cell infusion

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: Faron Pharmaceuticals Ltd
• Investigators: Principal Investigator: Jordan Gauthier, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Lymphoma; Lymphoma, B-Cell; Leukemia; Recurrence; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta
• Other Study ID Numbers: RG1123521; NCI-2023-04888 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 20021 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No