FT538 in Subjects With Advanced Hematologic Malignancies
- Conditions
- AML, AdultAcute Myeloid LeukemiaMultiple MyelomaMyeloma
- Interventions
- Registration Number
- NCT04614636
- Lead Sponsor
- Fate Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 42
-
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
-
-
Capable of giving signed informed consent
-
Agreement to comply with study procedures as described in the Schedule of Activities
-
Agrees to contraceptive use as described in the protocol
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Females who are pregnant or breastfeeding
-
ECOG Performance Status ≥ 2
-
Evidence of insufficient hematologic function as defined in the protocol
-
Evidence of insufficient organ function defined as defined by the protocol
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Clinically significant cardiovascular disease as defined by the protocol
-
Known active central nervous system (CNS) involvement by malignancy
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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
-
Currently receiving or likely to require systemic immunosuppressive therapy for any reason during the treatment period
-
Clinically significant infections including HIV, HBV and HCV
-
Live vaccine <6 weeks prior to start of lympho-conditioning
-
Receipt of an allograft organ transplant
-
Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host therapy
-
Known allergy to albumin (human) or DMSO
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Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject
-
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)
-
Diagnosis of promyelocytic leukemia with t(15;17) translocation
-
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)
-
Plasma cell leukemia defined as a plasma cell count >2000/mm3
-
Leptomeningeal involvement of MM
-
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
-
Allergy or hypersensitivity to antibodies or antibody-related proteins
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FT538 in Combination with Daratumumab FT538 FT538 in combination with daratumumab in subjects with r/r MM FT538 in Combination with Daratumumab Fludarabine FT538 in combination with daratumumab in subjects with r/r MM FT538 in Combination with Elotuzumab Cyclophosphamide FT538 in combination with elotuzumab in subjects with r/r MM FT538 in Combination with Elotuzumab FT538 FT538 in combination with elotuzumab in subjects with r/r MM FT538 Monotherapy FT538 FT538 monotherapy in subjects with r/r AML FT538 Monotherapy Cyclophosphamide FT538 monotherapy in subjects with r/r AML FT538 in Combination with Daratumumab Cyclophosphamide FT538 in combination with daratumumab in subjects with r/r MM FT538 Monotherapy Fludarabine FT538 monotherapy in subjects with r/r AML FT538 in Combination with Daratumumab Daratumumab FT538 in combination with daratumumab in subjects with r/r MM FT538 in Combination with Elotuzumab Fludarabine FT538 in combination with elotuzumab in subjects with r/r MM FT538 in Combination with Elotuzumab Elotuzumab FT538 in combination with elotuzumab in subjects with r/r MM
- Primary Outcome Measures
Name Time Method Incidence of dose-limiting toxicities (DLTs) within each dose level cohort Cycle 1, Up to Day 29 Nature of dose-limiting toxicities within each dose level cohort Cycle 1, Up to Day 29
- Secondary Outcome Measures
Name Time Method 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
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
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 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
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
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
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
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
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
Trial Locations
- Locations (8)
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
University of Minnesota Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Sarah Cannon Research Institute at Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
St. David's South Austin Medical Center
🇺🇸Austin, Texas, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States