FT538 in Subjects With Advanced Hematologic Malignancies

Sponsor
Fate Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04614636
Collaborator
(none)
105
Enrollment
7
Locations
3
Arms
213.5
Anticipated Duration (Months)
15
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase I dose-finding study of FT538 as monotherapy in acute myeloid leukemia (AML) and in combination with monoclonal antibodies in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
105 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Open-Label, Multicenter Study of FT538 as Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination With Monoclonal Antibodies in Relapsed/Refractory Multiple Myeloma
Actual Study Start Date :
Oct 17, 2020
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Aug 1, 2038

Arms and Interventions

ArmIntervention/Treatment
Experimental: FT538 Monotherapy

FT538 monotherapy in subjects with r/r AML

Drug: FT538
Experimental Interventional Therapy

Drug: Cyclophosphamid
Lympho-conditioning Agent

Drug: Fludarabine
Lympho-conditioning Agent

Experimental: FT538 in Combination with Daratumumab

FT538 in combination with daratumumab in subjects with r/r MM

Drug: FT538
Experimental Interventional Therapy

Drug: Cyclophosphamid
Lympho-conditioning Agent

Drug: Fludarabine
Lympho-conditioning Agent

Drug: Daratumumab
Monoclonal Antibody
Other Names:
  • Darzalex
  • Experimental: FT538 in Combination with Elotuzumab

    FT538 in combination with elotuzumab in subjects with r/r MM

    Drug: FT538
    Experimental Interventional Therapy

    Drug: Cyclophosphamid
    Lympho-conditioning Agent

    Drug: Fludarabine
    Lympho-conditioning Agent

    Drug: Elotuzumab
    Monoclonal Antibody
    Other Names:
  • Empliciti
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of dose-limiting toxicities within each dose level cohort [Cycle 1, Day 29]

    2. Nature of dose-limiting toxicities within each dose level cohort [Cycle 1, Day 29]

    Secondary Outcome Measures

    1. Incidence, nature, and severity of adverse events (AEs) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r multiple myeloma [Up to 5 years]

    2. Objective response rate (ORR) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM [From baseline tumor assessment up to approximately 2 years after last dose of FT538]

      Proportion of subjects who achieve a CR, CRMRD-, CRi, MLFS, or PR, as determined by the investigator according to 2017 ELN criteria for AML, and the proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG for MM response criteria

    3. Duration of response (DOR) of FT538 in combination with daratumumab or elotuzumab in r/r MM [Up to 15 years]

      Defined as the duration from the first occurrence of a documented objective response until the time of disease progression or relapse, or death due to progressive disease, as determined by the investigator according to standard IMWG response criteria

    4. Progression-free survival (PFS) of FT538 in combination with daratumumab or elotuzumab in r/r MM [Up to 15 years]

      Defined as the time from first dose of study treatment to disease progression or relapse, or to the day of death from any cause, as determined by the investigator according to standard IMWG response criteria

    5. Relapse-free survival (RFS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM [Up to 15 years]

      Defined as the time from initial CR (including CRMRD-, CR, and CRi) to hematologic relapse or death due to any cause, as determined by the investigator according to 2017 ELN criteria for AML, and defined as the duration from the start of sCR or CR until the time of relapse from sCR or CR, as determined by the investigator according to standard IMWG response criteria for MM

    6. Event-free survival (EFS) of FT538 as monotherapy in r/r AML [Up to 15 years]

      defined as the time from first dose of lympho-conditioning to the date of PD, or relapse from CR or CRi, or death from any cause, according to 2017 ELN criteria

    7. Overall survival (OS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM [Up to 15 years]

      defined as the time from first dose of lympho-conditioning to death from any cause

    8. Time-to-best response of FT538 as monotherapy in r/r AML [Up to 15 years]

      defined as the time from first dose of lympho-conditioning to best response

    9. Determination of the pharmacokinetics (PK) of FT538 cells in peripheral blood [Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29]

      The PK of FT538 in peripheral blood will be reported as the relative percentage of product (FT538) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Diagnosis of one of the following by treatment regimen:

    Regimen A (FT538 monotherapy in r/r AML)

    • Primary refractory AML, or

    • Relapsed AML, defined as not in CR after one or more re-induction attempts; if

    60 years of age, prior re-induction therapy is not required

    Regimens B or C (FT538 + mAb in r/r MM)

    • Regimen B only: MM that has relapsed or progressed after at least two lines of therapies, including a proteasome inhibitor and an immunomodulatory drug

    • Regimen C only: MM that has relapsed or progressed after proteasome inhibitor therapy, and immunomodulatory therapy

    • Regimen B and Regimen C: Measurable disease as defined in the protocol

    1. Capable of giving signed informed consent

    2. Age ≥18 years old

    3. Agreement to comply with study procedures as described in the Schedule of Activities

    4. Contraceptive use as described in the protocol

    Exclusion Criteria:
    1. Females who are pregnant or breastfeeding

    2. ECOG Performance Status ≥ 2

    3. Evidence of insufficient hematologic function as defined in the protocol

    4. Evidence of insufficient organ function defined as defined by the protocol

    5. Clinically significant cardiovascular disease as defined by the protocol

    6. Known active central nervous system (CNS) involvement by malignancy

    7. Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment

    8. Currently receiving or likely to require systemic immunosuppressive therapy for any reason during the treatment period

    9. Clinically significant infections including HIV, HBV and HCV

    10. Live vaccine <6 weeks prior to start of lympho-conditioning

    11. Receipt of an allograft organ transplant

    12. Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy

    13. Known allergy to albumin (human) or DMSO

    14. Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject

    15. Any medical condition or clinical laboratory abnormality that per investigator or Medical Monitor judgement precludes safe participation in and completion of the study, or which could affect compliance with protocol conduct or interpretation of results

    Exclusion Criteria Specific to Regimen A (r/r AML)

    1. Diagnosis of promyelocytic leukemia with t(15;17) translocation

    2. Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1

    Exclusion Criteria Specific to Regimens B and C (r/r MM)

    1. Plasma cell leukemia defined as a plasma cell count >2000/mm3

    2. Leptomeningeal involvement of MM

    3. Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the first dose of mAb

    4. Allergy or hypersensitivity to antibodies or antibody-related proteins

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Minnesota Masonic Cancer CenterMinneapolisMinnesotaUnited States55455
    2Washington UniversitySaint LouisMissouriUnited States63110
    3Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    4Tennessee Oncology NashvilleNashvilleTennesseeUnited States37203
    5St. David's South Austin Medical CenterAustinTexasUnited States78704
    6MD Anderson Cancer CenterHoustonTexasUnited States77030
    7Texas Transplant InstituteSan AntonioTexasUnited States78229

    Sponsors and Collaborators

    • Fate Therapeutics

    Investigators

    • Study Director: John Byon, MD, Fate Therapeutics, Inc

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Fate Therapeutics
    ClinicalTrials.gov Identifier:
    NCT04614636
    Other Study ID Numbers:
    • FT538-101
    First Posted:
    Nov 4, 2020
    Last Update Posted:
    Oct 5, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Fate Therapeutics
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 5, 2021