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

Primary Purpose

Recurrent B Acute Lymphoblastic Leukemia, Recurrent B-Cell Non-Hodgkin Lymphoma, Refractory B Acute Lymphoblastic Leukemia

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Interferon Beta-1A
X-Ray Imaging
Echocardiography
Multigated Acquisition Scan
Computed Tomography
Positron Emission Tomography
Lumbar Puncture
Bone Marrow Aspiration
Bone Marrow Biopsy
Biospecimen Collection
Biopsy
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Recurrent B Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm 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.

Outcomes

Primary Outcome Measures

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%.
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.

Secondary Outcome Measures

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.
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.
Cumulative corticosteroids dose
Will be summarized using descriptive statistics (median, quantiles) based on the CRS and ICANS analysis set.
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.
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.

Full Information

First Posted
June 30, 2023
Last Updated
July 6, 2023
Sponsor
Fred Hutchinson Cancer Center
Collaborators
Faron Pharmaceuticals Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05936229
Brief Title
Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
November 30, 2026 (Anticipated)
Study Completion Date
November 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
Faron Pharmaceuticals Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Prevention (interferon beta-1A [FP-1201])
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Interferon Beta-1A
Other Intervention Name(s)
145258-61-3, Avonex, BG9418, Rebif, Recombinant interferon beta-1a
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
X-Ray Imaging
Other Intervention Name(s)
Conventional X-Ray, Diagnostic Radiology, Medical Imaging, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray
Intervention Description
Undergo x-ray
Intervention Type
Procedure
Intervention Name(s)
Echocardiography
Other Intervention Name(s)
EC
Intervention Description
Undergo ECHO
Intervention Type
Procedure
Intervention Name(s)
Multigated Acquisition Scan
Other Intervention Name(s)
Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning
Intervention Description
Undergo MUGA
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT Scan, Computed Axial Tomography, Computerized axial tomography (procedure)
Intervention Description
Undergo CT
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Pet Scan, Positron emission tomography (procedure), Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Intervention Description
Undergo PET/CT
Intervention Type
Procedure
Intervention Name(s)
Lumbar Puncture
Other Intervention Name(s)
LP, spinal tap
Intervention Description
Undergo LP
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Aspiration
Intervention Description
Undergo bone marrow aspiration
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Biopsy
Intervention Description
Undergo bone marrow biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection
Intervention Description
Undergo blood and CSF sample collection
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo tissue biopsy
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT) rates
Description
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%.
Time Frame
Within 14 days after the last administration of interferon-beta-1a (FP-1201)
Title
Incidence of adverse events (AEs)
Description
Type, frequency, and severity of AEs according to the National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0.
Time Frame
From the first dose of FP-1201 through day 28 after chimeric antigen receptor (CAR) T-cell infusion
Secondary Outcome Measure Information:
Title
Cytokine release syndrome (CRS) rates
Description
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.
Time Frame
From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last
Title
Immune effector cell associated-neurotoxicity syndrome (ICANS) rates
Description
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.
Time Frame
From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last
Title
Cumulative corticosteroids dose
Description
Will be summarized using descriptive statistics (median, quantiles) based on the CRS and ICANS analysis set.
Time Frame
Within 28 days after CAR T-cell infusion
Title
Overall response rate
Description
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.
Time Frame
28 days after CAR T-cell infusion
Title
Complete response rate
Description
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.
Time Frame
28 days after CAR T-cell infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fred Hutch Immunotherapy Intake
Phone
206-606-4668
Email
immunotherapy@fredhutch.org
First Name & Middle Initial & Last Name or Official Title & Degree
Fred Hutch Immunotherapy Intake
Phone
855-557-0555
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jordan Gauthier
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fred Hutch Immunotherapy Intake
Phone
206-606-4668
Email
immunotherapy@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Fred Hutch Immunotherapy Intake
Phone
855-557-0555
First Name & Middle Initial & Last Name & Degree
Jordan Gauthier

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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