Clinical trial NCT04614636: FT538 in Subjects With Advanced Hematologic Malignancies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
AML, Adult
Multiple Myeloma
Myeloma
Keywords: Acute Myeloid Leukemia
AML
Multiple Myeloma
daratumumab
elotuzumab
NK cell
cellular therapy
allogeneic cell therapy
allogeneic cellular therapy
CD38
Anti-CD38
Lead sponsor: Fate Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-11-04
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs) within each dose level cohort
timeFrame: Cycle 1, Up to Day 29
measure: Nature of dose-limiting toxicities within each dose level cohort
timeFrame: Cycle 1, Up to Day 29
Secondary outcomes:
measure: 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
timeFrame: Up to 5 years
measure: Objective response rate (ORR) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM
timeFrame: From baseline tumor assessment up to approximately 2 years after last dose of FT538
measure: Duration of response (DOR) of FT538 in combination with daratumumab or elotuzumab in r/r MM
timeFrame: Up to 15 years
measure: Progression-free survival (PFS) of FT538 in combination with daratumumab or elotuzumab in r/r MM
timeFrame: Up to 15 years
measure: Relapse-free survival (RFS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM
timeFrame: Up to 15 years
measure: Event-free survival (EFS) of FT538 as monotherapy in r/r AML
timeFrame: Up to 15 years
measure: Overall survival (OS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM
timeFrame: Up to 15 years
measure: Time-to-best response of FT538 as monotherapy in r/r AML
timeFrame: Up to 15 years
measure: Determination of the pharmacokinetics (PK) of FT538 cells in peripheral blood
timeFrame: Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
Study officials:
affiliation: Fate Therapeutics, Inc
name: Fate Trial Disclosure
role: STUDY_DIRECTOR
References: