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FT576 in Subjects With Multiple Myeloma

Primary Purpose

Multiple Myeloma, Myeloma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
FT576 (Allogenic CAR NK cells with BCMA expression)
Cyclophosphamide
Fludarabine
Daratumumab
Bendamustine
Sponsored by
Fate Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, daratumumab, CAR NK cell, cellular therapy, relapsed/refractory multiple myeloma, allogeneic natural killer cells, anti-CD38 monoclonal antibody, chimeric antigen receptor (CAR), BCMA, anti-B-cell maturation antigen (BCMA), natural killer (NK) cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • Abbreviated inclusion criteria:

Diagnosis of r/r MM with measurable disease by at least one of the following:

  • Serum M-protein ≥1.0 g/dL
  • Urine M-protein ≥200 mg/24 hours
  • Involved serum free light chain level ≥10 mg/dL, with an abnormal kappa-lambda ratio if the serum M-protein <1.0 g/dL and/or urine M-protein <200 mg/24 hours
  • Regimens A and A1: MM relapsed or progressed after ≥3 prior approved therapies, including an IMiD, proteosome inhibitor, and anti-CD38 mAb
  • Regimens B and B1: MM relapsed or progressed after ≥2 prior approved therapies, including an IMiD and proteosome inhibitor

Note: for all Regimens, prior BCMA CAR T-cell therapy and BCMA-targeted therapy (e.g., bi-specific engagers or antibody-drug conjugates) is allowed

* Abbreviated exclusion criteria:

Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2

Evidence of insufficient hematologic function:

  • ANC <1000/µL without growth factor support ≤7 days prior to measurement
  • Platelet count <75,000/µL without platelet transfusion ≤72 hours prior to measurement

Evidence of insufficient organ function

  • CrCL <50 ml/min by Cockcroft-Gault or other institutional method
  • T bilirubin >1.5x ULN, except for Gilbert's syndrome
  • AST >3x ULN or ALT >3x ULN, unless directly due to underlying malignancy
  • O2 sat <92% on room air

Clinically significant cardiovascular disease:

  • Myocardial infarction within 6 months of first treatment
  • Unstable angina or CHF of NYHA Grade 2 or higher
  • Cardiac EF <40%

Subjects with active central nervous system (CNS) , including leptomeningeal disease. Subjects with prior CNS involvement may be enrolled into the study if effective treatment of their CNS disease was completed at least 3 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging.

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

Currently receiving or likely to require immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason during the treatment period, with the exception of corticosteroids.

Clinically significant infections, including:

  • HIV positive by serology
  • HBV positive by serology or PCR
  • HCV positive by serology or PCR

Live vaccine <6 weeks prior to start of conditioning

Receipt of an allograft organ transplant

Ongoing requirement for systemic graft -versus-host disease therapy

Plasma cell leukemia defined as a plasma cell count >2000/mm^3

Prior malignancy (other than current indication including any antecedent hematologic disorder) within the 2 years prior to enrollment except for the following: basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix or breast treated with curative intent, or localized prostate cancer treated with curative intent, or malignancy that, in the opinion of the investigator and Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years.

Washout periods from prior therapies:

  • For all subjects (Regimens A, A1, B and B1), receipt of the following: Chemotherapy, or radiation therapy, except for palliative purposes, within 14 days prior to the first dose of FT576 (Day 1) or five half-lives, whichever is shorter; Investigational therapy within 30 days prior to the first dose of FT576 study treatment or five half-lives, whichever is shorter; Biologic therapy (except for anti-CD38 mAbs in Regimen B and B1), including autologous cellular immunotherapy (e.g. CAR-T/ CAR-NK), antibody-drug conjugates or bi-specific immune-cell engaging antibody within 30 days prior to first dose of FT576 (Day 1) or half -lives whichever is shorter. prior allogenic HSCT or allogenic CAR-T/CAR-NK within 6 months of first dose of FT576 (Day1).
  • For subjects in Regimens B and B1 only, receipt of the following: Anti-CD38 therapy alone or in combination within 3 months prior to the start of daratumumab

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • City of HopeRecruiting
  • Colorado Blood Cancer InstituteRecruiting
  • Medical Oncology Hematology Consultants, PARecruiting
  • Indiana University Melvin and Bern Simon Comprehensive Cancer CenterRecruiting
  • Oncology Hematology Care, IncRecruiting
  • Tennessee Oncology - NashvilleRecruiting
  • Texas Oncology-Medical City DallasRecruiting
  • Virginia Oncology AssociatesRecruiting
  • Froedtert Hospital, Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Regimen A

Regimen A1

Regimen B

Regimen B1

Arm Description

FT576 single dose monotherapy in subjects with r/r MM

FT576 multiple dose monotherapy in subjects with r/r MM

FT576 single dose in combination with daratumumab in subjects with r/r MM

FT576 multiple dose in combination with daratumumab in subjects with r/r MM

Outcomes

Primary Outcome Measures

Incidence and nature of DLTs within each dose-escalation cohort to determine the MTD or MAD
Determine the RP2D which will be based on the overall safety and anti-tumor activity among the dose escalation and dose expansion cohorts
Incidence, nature, and severity of adverse events

Secondary Outcome Measures

Objective response rate (ORR)
Proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG response criteria
Duration of response (DOR)
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)
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) from complete response (CR)
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
Overall survival (OS)
Time from first dose of study treatment to death from any cause
Pharmacokinetics (PK) of FT576
Concentration of FT576 in peripheral blood following FT576 administration

Full Information

First Posted
October 15, 2021
Last Updated
May 1, 2023
Sponsor
Fate Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05182073
Brief Title
FT576 in Subjects With Multiple Myeloma
Official Title
A Phase I Study of FT576 as Monotherapy and in Combination With Daratumumab in Subjects With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 24, 2021 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
February 2040 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fate Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase I dose-finding study of FT576 as monotherapy and in combination with the monoclonal antibody daratumumab in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Myeloma
Keywords
Multiple Myeloma, daratumumab, CAR NK cell, cellular therapy, relapsed/refractory multiple myeloma, allogeneic natural killer cells, anti-CD38 monoclonal antibody, chimeric antigen receptor (CAR), BCMA, anti-B-cell maturation antigen (BCMA), natural killer (NK) cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
168 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Regimen A
Arm Type
Experimental
Arm Description
FT576 single dose monotherapy in subjects with r/r MM
Arm Title
Regimen A1
Arm Type
Experimental
Arm Description
FT576 multiple dose monotherapy in subjects with r/r MM
Arm Title
Regimen B
Arm Type
Experimental
Arm Description
FT576 single dose in combination with daratumumab in subjects with r/r MM
Arm Title
Regimen B1
Arm Type
Experimental
Arm Description
FT576 multiple dose in combination with daratumumab in subjects with r/r MM
Intervention Type
Drug
Intervention Name(s)
FT576 (Allogenic CAR NK cells with BCMA expression)
Intervention Description
Experimental Interventional Therapy: FT576 comprises allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, human-induced pluripotent stem cell line (iPSC) that expresses anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR), high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF).
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Conditioning Agent
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Conditioning Agent
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Darzalex, Darzalex Faspro
Intervention Description
Anti-CD38 Monoclonal Antibody
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Bendeka, Treanda
Intervention Description
Conditioning Agent
Primary Outcome Measure Information:
Title
Incidence and nature of DLTs within each dose-escalation cohort to determine the MTD or MAD
Time Frame
Cycle 1 Day -5 to Day 29 for Regimen A and A1; Cycle 1 Day -11 to Day 29 (each cycle is 40 days) for Regimen B and B1
Title
Determine the RP2D which will be based on the overall safety and anti-tumor activity among the dose escalation and dose expansion cohorts
Time Frame
From FPI to LPI's end of Cycle 1 study treatment (End of cycle is Day 29 from Day 1 FT576 infusion)
Title
Incidence, nature, and severity of adverse events
Time Frame
Cycle 1 Day -5 to Day 29 for Regimen A and A1; Cycle 1 Day -11 to Day 29 (each cycle is 40 days) for Regimen B and B1
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG response criteria
Time Frame
From baseline tumor assessment up to approximately 2 years after last dose of FT576
Title
Duration of response (DOR)
Description
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
Time Frame
Up to 15 years
Title
Progression-free survival (PFS)
Description
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
Time Frame
Up to 15 years
Title
Relapse-free survival (RFS) from complete response (CR)
Description
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
Time Frame
Up to 15 years
Title
Overall survival (OS)
Description
Time from first dose of study treatment to death from any cause
Time Frame
Up to 15 years
Title
Pharmacokinetics (PK) of FT576
Description
Concentration of FT576 in peripheral blood following FT576 administration
Time Frame
From Baseline to PTFU visit of last cycle on the study treatment (End of cycle is Day 29 from Day 1 FT576 infusion of this cycle)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Abbreviated inclusion criteria: Diagnosis of r/r MM with measurable disease by at least one of the following: Serum M-protein ≥1.0 g/dL Urine M-protein ≥200 mg/24 hours Involved serum free light chain level ≥10 mg/dL, with an abnormal kappa-lambda ratio if the serum M-protein <1.0 g/dL and/or urine M-protein <200 mg/24 hours Regimens A and A1: MM relapsed or progressed after ≥3 prior approved therapies, including an IMiD, proteosome inhibitor, and anti-CD38 mAb Regimens B and B1: MM relapsed or progressed after ≥2 prior approved therapies, including an IMiD and proteosome inhibitor Note: for all Regimens, prior BCMA CAR T-cell therapy and BCMA-targeted therapy (e.g., bi-specific engagers or antibody-drug conjugates) is allowed * Abbreviated exclusion criteria: Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 Evidence of insufficient hematologic function: ANC <1000/µL without growth factor support ≤7 days prior to measurement Platelet count <75,000/µL without platelet transfusion ≤72 hours prior to measurement Evidence of insufficient organ function CrCL <50 ml/min by Cockcroft-Gault or other institutional method T bilirubin >1.5x ULN, except for Gilbert's syndrome AST >3x ULN or ALT >3x ULN, unless directly due to underlying malignancy O2 sat <92% on room air Clinically significant cardiovascular disease: Myocardial infarction within 6 months of first treatment Unstable angina or CHF of NYHA Grade 2 or higher Cardiac EF <40% Subjects with active central nervous system (CNS) , including leptomeningeal disease. Subjects with prior CNS involvement may be enrolled into the study if effective treatment of their CNS disease was completed at least 3 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging. 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 Currently receiving or likely to require immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason during the treatment period, with the exception of corticosteroids. Clinically significant infections, including: HIV positive by serology HBV positive by serology or PCR HCV positive by serology or PCR Live vaccine <6 weeks prior to start of conditioning Receipt of an allograft organ transplant Ongoing requirement for systemic graft -versus-host disease therapy Plasma cell leukemia defined as a plasma cell count >2000/mm^3 Prior malignancy (other than current indication including any antecedent hematologic disorder) within the 2 years prior to enrollment except for the following: basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix or breast treated with curative intent, or localized prostate cancer treated with curative intent, or malignancy that, in the opinion of the investigator and Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years. Washout periods from prior therapies: For all subjects (Regimens A, A1, B and B1), receipt of the following: Chemotherapy, or radiation therapy, except for palliative purposes, within 14 days prior to the first dose of FT576 (Day 1) or five half-lives, whichever is shorter; Investigational therapy within 30 days prior to the first dose of FT576 study treatment or five half-lives, whichever is shorter; Biologic therapy (except for anti-CD38 mAbs in Regimen B and B1), including autologous cellular immunotherapy (e.g. CAR-T/ CAR-NK), antibody-drug conjugates or bi-specific immune-cell engaging antibody within 30 days prior to first dose of FT576 (Day 1) or half -lives whichever is shorter. prior allogenic HSCT or allogenic CAR-T/CAR-NK within 6 months of first dose of FT576 (Day1). For subjects in Regimens B and B1 only, receipt of the following: Anti-CD38 therapy alone or in combination within 3 months prior to the start of daratumumab
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fate Trial Disclosure
Phone
866-875-1800
Email
FateTrialDisclosure@fatetherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fate Trial Disclosure
Organizational Affiliation
Fate Therapeutics, Inc
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Individual Site Status
Recruiting
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical Oncology Hematology Consultants, PA
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Individual Site Status
Recruiting
Facility Name
Indiana University Melvin and Bern Simon Comprehensive Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Name
Oncology Hematology Care, Inc
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology - Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology-Medical City Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Individual Site Status
Recruiting
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Individual Site Status
Recruiting
Facility Name
Froedtert Hospital, Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://ash.confex.com/ash/2020/webprogram/Paper142750.html
Description
ASH Dec 2020 Abstract

Learn more about this trial

FT576 in Subjects With Multiple Myeloma

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