FT538 in Subjects With Advanced Hematologic Malignancies

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04614636
• Other study ID #: FT538-101
• Status: Terminated
• Phase: Phase 1
• Start date: October 17, 2020
• Est. completion date: August 8, 2023

Study information

• Verified date: September 2023
• Source: Fate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: August 8, 2023
• Est. primary completion date: July 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

17. 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)

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

19. Leptomeningeal involvement of MM

20. 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

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• AML, Adult
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Multiple Myeloma
• Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• FT538
Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell
• Cyclophosphamide
Lympho-conditioning Agent
• Fludarabine
Lympho-conditioning Agent
• Daratumumab
Monoclonal Antibody, CD38, Anti-CD38
• Elotuzumab
Monoclonal Antibody

Locations

Country	Name	City	State
United States	St. David's South Austin Medical Center	Austin	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University	Saint Louis	Missouri
United States	Texas Transplant Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs) within each dose level cohort		Cycle 1, Up to Day 29
Primary	Nature of dose-limiting toxicities within each dose level cohort		Cycle 1, Up to Day 29
Secondary	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
Secondary	Objective response rate (ORR) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM	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	From baseline tumor assessment up to approximately 2 years after last dose of FT538
Secondary	Duration of response (DOR) of FT538 in combination with daratumumab or elotuzumab in r/r MM	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	Up to 15 years
Secondary	Progression-free survival (PFS) of FT538 in combination with daratumumab or elotuzumab in r/r MM	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	Up to 15 years
Secondary	Relapse-free survival (RFS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM	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	Up to 15 years
Secondary	Event-free survival (EFS) of FT538 as monotherapy in r/r AML	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	Up to 15 years
Secondary	Overall survival (OS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM	defined as the time from first dose of lympho-conditioning to death from any cause	Up to 15 years
Secondary	Time-to-best response of FT538 as monotherapy in r/r AML	defined as the time from first dose of lympho-conditioning to best response	Up to 15 years
Secondary	Determination of the pharmacokinetics (PK) of FT538 cells in peripheral blood	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	Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29

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