FT538 in Subjects With Advanced Hematologic Malignancies

• ClinicalTrials.gov Identifier: NCT04614636
• Recruitment Status: Recruiting
• First Posted: November 4, 2020
• Last Update Posted: May 25, 2022
• Sponsor: Fate Therapeutics
• Information provided by (Responsible Party): Fate Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia; AML, Adult; Multiple Myeloma; Myeloma	Drug: FT538; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Daratumumab; Drug: Elotuzumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 105 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 17, 2020
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: August 2038

Arms and Interventions

Arm	Intervention/treatment
Experimental: FT538 Monotherapy; FT538 monotherapy in subjects with r/r AML	Drug: FT538; Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell; Drug: Cyclophosphamide; Lympho-conditioning Agent; Drug: Fludarabine; Lympho-conditioning Agent
Experimental: FT538 in Combination with Daratumumab; FT538 in combination with daratumumab in subjects with r/r MM	Drug: FT538; Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell; Drug: Cyclophosphamide; Lympho-conditioning Agent; Drug: Fludarabine; Lympho-conditioning Agent; Drug: Daratumumab; Monoclonal Antibody, CD38, Anti-CD38; Other Name: Darzalex
Experimental: FT538 in Combination with Elotuzumab; FT538 in combination with elotuzumab in subjects with r/r MM	Drug: FT538; Experimental Interventional Therapy, Allogeneic Cell Therapy NK Cell; Drug: Cyclophosphamide; Lympho-conditioning Agent; Drug: Fludarabine; Lympho-conditioning Agent; Drug: Elotuzumab; Monoclonal Antibody; Other Name: Empliciti

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting toxicities within each dose level cohort [ Time Frame: Cycle 1, Day 29 ]
2. Nature of dose-limiting toxicities within each dose level cohort [ Time Frame: Cycle 1, Day 29 ]

Secondary Outcome Measures :

1. 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 ]
2. 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 ]
   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
3. Duration of response (DOR) of FT538 in combination with daratumumab or elotuzumab in r/r MM [ Time Frame: 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
4. Progression-free survival (PFS) of FT538 in combination with daratumumab or elotuzumab in r/r MM [ Time Frame: 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
5. 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 ]
   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
6. Event-free survival (EFS) of FT538 as monotherapy in r/r AML [ Time Frame: 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
7. 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 ]
   defined as the time from first dose of lympho-conditioning to death from any cause
8. Time-to-best response of FT538 as monotherapy in r/r AML [ Time Frame: Up to 15 years ]
   defined as the time from first dose of lympho-conditioning to best response
9. Determination of the pharmacokinetics (PK) of FT538 cells in peripheral blood [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Mohamed Elgendy; 8588751800; clinical@fatetherapeutics.com

Contact: Dennis Hazekamp; 8588751800; clinical@fatetherapeutics.com

Locations

United States, Colorado

Colorado Blood Cancer Institute; Recruiting

Denver, Colorado, United States, 80218

United States, Minnesota

University of Minnesota Masonic Cancer Center; Recruiting

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Washington University; Recruiting

Saint Louis, Missouri, United States, 63110

United States, New Jersey

John Theurer Cancer Center at Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

United States, Tennessee

Tennessee Oncology Nashville; Recruiting

Nashville, Tennessee, United States, 37203

United States, Texas

St. David's South Austin Medical Center; Recruiting

Austin, Texas, United States, 78704

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Texas Transplant Institute; Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Fate Therapeutics

Investigators

• Study Director: John Byon, MD; Fate Therapeutics, Inc

More Information

Additional Information:

Related Info 

• Responsible Party: Fate Therapeutics
• ClinicalTrials.gov Identifier: NCT04614636
• Other Study ID Numbers: FT538-101
• First Posted: November 4, 2020
• Last Update Posted: May 25, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fate Therapeutics:

Acute Myeloid Leukemia; AML; Multiple Myeloma; daratumumab; elotuzumab; NK cell; cellular therapy; allogeneic cell therapy; allogeneic cellular therapy; CD38; Anti-CD38

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Cyclophosphamide; Fludarabine; Daratumumab; Elotuzumab; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists