Clinical Trials /

FT538 in Subjects With Advanced Hematologic Malignancies

NCT04614636

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: FT538-101
  • NCT ID: NCT04614636

Conditions

  • Acute Myeloid Leukemia
  • AML, Adult
  • Multiple Myeloma
  • Myeloma

Interventions

DrugSynonymsArms
FT538FT538 Monotherapy
CyclophosphamidFT538 Monotherapy
FludarabineFT538 Monotherapy
DaratumumabDarzalexFT538 in Combination with Daratumumab
ElotuzumabEmplicitiFT538 in Combination with Elotuzumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
FT538 MonotherapyExperimentalFT538 monotherapy in subjects with r/r AML
  • FT538
  • Cyclophosphamid
  • Fludarabine
FT538 in Combination with DaratumumabExperimentalFT538 in combination with daratumumab in subjects with r/r MM
  • FT538
  • Cyclophosphamid
  • Fludarabine
  • Daratumumab
FT538 in Combination with ElotuzumabExperimentalFT538 in combination with elotuzumab in subjects with r/r MM
  • FT538
  • Cyclophosphamid
  • Fludarabine
  • Elotuzumab

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. Age ≥18 years old

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

          5. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities within each dose level cohort
Time Frame:Cycle 1, Day 29
Safety Issue:
Description:

Secondary Outcome Measures

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
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Objective response rate (ORR) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM
Time Frame:From baseline tumor assessment up to approximately 2 years after last dose of FT538
Safety Issue:
Description: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
Measure:Duration of response (DOR) of FT538 in combination with daratumumab or elotuzumab in r/r MM
Time Frame:Up to 15 years
Safety Issue:
Description: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
Measure:Progression-free survival (PFS) of FT538 in combination with daratumumab or elotuzumab in r/r MM
Time Frame:Up to 15 years
Safety Issue:
Description: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
Measure:Relapse-free survival (RFS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM
Time Frame:Up to 15 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS) of FT538 as monotherapy in r/r AML
Time Frame:Up to 15 years
Safety Issue:
Description: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
Measure:Overall survival (OS) of FT538 as monotherapy in r/r AML and in combination with daratumumab or elotuzumab in r/r MM
Time Frame:Up to 15 years
Safety Issue:
Description:defined as the time from first dose of lympho-conditioning to death from any cause
Measure:Time-to-best response of FT538 as monotherapy in r/r AML
Time Frame:Up to 15 years
Safety Issue:
Description:defined as the time from first dose of lympho-conditioning to best response
Measure:Determination of the pharmacokinetics (PK) of FT538 cells in peripheral blood
Time Frame:Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fate Therapeutics

Trial Keywords

  • Acute Myeloid Leukemia
  • AML
  • Multiple Myeloma
  • daratumumab
  • elotuzumab
  • NK cell
  • cellular therapy

Last Updated

November 4, 2020