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

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Withdrawn

Phase 2

Phase 1

Conditions

Refractory B Acute Lymphoblastic Leukemia

Refractory B-Cell Non-Hodgkin Lymphoma

Recurrent Mantle Cell Lymphoma

Recurrent B-Cell Non-Hodgkin Lymphoma

Refractory Mantle Cell Lymphoma

Recurrent B Acute Lymphoblastic Leukemia

Treatments

Procedure: Biospecimen Collection

Procedure: Echocardiography

Procedure: Bone Marrow Biopsy

Biological: Interferon Beta-1A

Procedure: Positron Emission Tomography

Procedure: Biopsy

Procedure: Computed Tomography

Procedure: Lumbar Puncture

Procedure: Bone Marrow Aspiration

Procedure: Multigated Acquisition Scan

Procedure: X-Ray Imaging

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05936229

20021 (Other Identifier)

NCI-2023-04888 (Registry Identifier)

RG1123521

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

0 participants in 1 patient group

Prevention (interferon beta-1A [FP-1201])

Experimental group

Description:

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.

Treatment: