Acute Myeloid Leukemia, AML, Adult, Multiple Myeloma, Myeloma
Conditions
Keywords
Acute Myeloid Leukemia, AML, Multiple Myeloma, daratumumab, elotuzumab, NK cell, cellular therapy, allogeneic cell therapy, allogeneic cellular therapy, CD38, Anti-CD38
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.
Interventions
DRUGFT538
Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell
DRUGCyclophosphamide
Lympho-conditioning Agent
DRUGFludarabine
Lympho-conditioning Agent
DRUGDaratumumab
Monoclonal Antibody, CD38, Anti-CD38
DRUGElotuzumab
Monoclonal Antibody
Sponsors
Fate Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 2. Capable of giving signed informed consent 3. Agreement to comply with study procedures as described in the Schedule of Activities 4. Agrees to 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 | — |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed