Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy
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| ClinicalTrials.gov Identifier: NCT05936229 |
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Recruitment Status :
Not yet recruiting
First Posted : July 7, 2023
Last Update Posted : May 9, 2024
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Sponsor:
Fred Hutchinson Cancer Center
Collaborator:
Faron Pharmaceuticals Ltd
Information provided by (Responsible Party):
Fred Hutchinson Cancer Center
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent B Acute Lymphoblastic Leukemia Recurrent B-Cell Non-Hodgkin Lymphoma Refractory B Acute Lymphoblastic Leukemia Refractory B-Cell Non-Hodgkin Lymphoma Recurrent Mantle Cell Lymphoma Refractory Mantle Cell Lymphoma | Biological: Interferon Beta-1A Procedure: X-Ray Imaging Procedure: Echocardiography Procedure: Multigated Acquisition Scan Procedure: Computed Tomography Procedure: Positron Emission Tomography Procedure: Lumbar Puncture Procedure: Bone Marrow Aspiration Procedure: Bone Marrow Biopsy Procedure: Biospecimen Collection Procedure: Biopsy | Phase 1 Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 24 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | 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 |
| Estimated Study Start Date : | April 1, 2025 |
| Estimated Primary Completion Date : | October 30, 2027 |
| Estimated Study Completion Date : | October 30, 2027 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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.
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Biological: Interferon Beta-1A
Given IV
Other Names:
Procedure: X-Ray Imaging Undergo x-ray
Other Names:
Procedure: Echocardiography Undergo ECHO
Other Name: EC Procedure: Multigated Acquisition Scan Undergo MUGA
Other Names:
Procedure: Computed Tomography Undergo CT
Other Names:
Procedure: Positron Emission Tomography Undergo PET/CT
Other Names:
Procedure: Lumbar Puncture Undergo LP
Other Names:
Procedure: Bone Marrow Aspiration Undergo bone marrow aspiration Procedure: Bone Marrow Biopsy Undergo bone marrow biopsy Procedure: Biospecimen Collection Undergo blood and CSF sample collection
Other Name: Biological Sample Collection Procedure: Biopsy Undergo tissue biopsy
Other Names:
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Primary Outcome Measures :
- Dose-limiting toxicity (DLT) rates [ Time Frame: Within 14 days after the last administration of interferon-beta-1a (FP-1201) ]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%.
- Incidence of adverse events (AEs) [ Time Frame: From the first dose of FP-1201 through day 28 after chimeric antigen receptor (CAR) T-cell infusion ]Type, frequency, and severity of AEs according to the National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0.
Secondary Outcome Measures :
- Cytokine release syndrome (CRS) rates [ Time Frame: From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last ]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.
- Immune effector cell associated-neurotoxicity syndrome (ICANS) rates [ Time Frame: From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last ]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.
- Cumulative corticosteroids dose [ Time Frame: Within 28 days after CAR T-cell infusion ]Will be summarized using descriptive statistics (median, quantiles) based on the CRS and ICANS analysis set.
- Overall response rate [ Time Frame: 28 days after CAR T-cell infusion ]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.
- Complete response rate [ Time Frame: 28 days after CAR T-cell infusion ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05936229
Contacts
| Contact: Fred Hutch Immunotherapy Intake | 206-606-4668 | immunotherapy@fredhutch.org | |
| Contact: Fred Hutch Immunotherapy Intake | 855-557-0555 |
Locations
| United States, Washington | |
| Fred Hutch/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Contact: Fred Hutch Immunotherapy Intake 206-606-4668 immunotherapy@fredhutch.org | |
| Contact: Fred Hutch Immunotherapy Intake 855-557-0555 | |
| Principal Investigator: Jordan Gauthier | |
Sponsors and Collaborators
Fred Hutchinson Cancer Center
Faron Pharmaceuticals Ltd
Investigators
| Principal Investigator: | Jordan Gauthier | Fred Hutch/University of Washington Cancer Consortium |
| Responsible Party: | Fred Hutchinson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT05936229 |
| 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 ) |
| First Posted: | July 7, 2023 Key Record Dates |
| Last Update Posted: | May 9, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Lymphoma Leukemia Lymphoma, Non-Hodgkin Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Mantle-Cell Lymphoma, B-Cell Recurrence Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Hematologic Diseases Disease Attributes Pathologic Processes Interferons Interferon-beta Interferon beta-1a Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs Adjuvants, Immunologic |