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Trial record 1 of 1 for:    ft-576
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FT576 in Subjects With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT05182073
Recruitment Status : Recruiting
First Posted : January 10, 2022
Last Update Posted : October 24, 2022
Sponsor:
Information provided by (Responsible Party):
Fate Therapeutics

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Myeloma Drug: FT576 (Allogenic CAR NK cells with BCMA expression) Drug: Cyclophosphamide Drug: Fludarabine Drug: Daratumumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of FT576 as Monotherapy and in Combination With Daratumumab in Subjects With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : November 24, 2021
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : February 2040

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
Experimental: Regimen A
FT576 single dose monotherapy in subjects with r/r MM
Drug: FT576 (Allogenic CAR NK cells with BCMA expression)
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).

Drug: Cyclophosphamide
Conditioning Agent

Drug: Fludarabine
Conditioning Agent

Experimental: Regimen A1
FT576 multiple dose monotherapy in subjects with r/r MM
Drug: FT576 (Allogenic CAR NK cells with BCMA expression)
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).

Drug: Cyclophosphamide
Conditioning Agent

Drug: Fludarabine
Conditioning Agent

Experimental: Regimen B
FT576 single dose in combination with daratumumab in subjects with r/r MM
Drug: FT576 (Allogenic CAR NK cells with BCMA expression)
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).

Drug: Cyclophosphamide
Conditioning Agent

Drug: Fludarabine
Conditioning Agent

Drug: Daratumumab
Anti-CD38 Monoclonal Antibody
Other Names:
  • Darzalex
  • Darzalex Faspro

Experimental: Regimen B1
FT576 multiple dose in combination with daratumumab in subjects with r/r MM
Drug: FT576 (Allogenic CAR NK cells with BCMA expression)
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).

Drug: Cyclophosphamide
Conditioning Agent

Drug: Fludarabine
Conditioning Agent

Drug: Daratumumab
Anti-CD38 Monoclonal Antibody
Other Names:
  • Darzalex
  • Darzalex Faspro




Primary Outcome Measures :
  1. 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 ]
  2. 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) ]
  3. 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 Measures :
  1. Objective response rate (ORR) [ Time Frame: From baseline tumor assessment up to approximately 2 years after last dose of FT576 ]
    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

  2. Duration of response (DOR) [ Time Frame: Up to 15 years ]
    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

  3. Progression-free survival (PFS) [ Time Frame: Up to 15 years ]
    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

  4. Relapse-free survival (RFS) from complete response (CR) [ Time Frame: Up to 15 years ]
    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

  5. Overall survival (OS) [ Time Frame: Up to 15 years ]
    Time from first dose of study treatment to death from any cause

  6. Pharmacokinetics (PK) of FT576 [ 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) ]
    Concentration of FT576 in peripheral blood following FT576 administration



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05182073


Contacts
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Contact: Kimberly Musni 8588751800 clinical@fatetherapeutics.com
Contact: Dennis Hazekamp 8588751800 clinical@fatetherapeutics.com

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
United States, Delaware
Medical Oncology Hematology Consultants, PA Recruiting
Newark, Delaware, United States, 19713
United States, Indiana
Indiana University Melvin and Bern Simon Comprehensive Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
United States, Ohio
Oncology Hematology Care, Inc Recruiting
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Tennessee Oncology - Nashville Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology-Medical City Dallas Recruiting
Dallas, Texas, United States, 75230
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
United States, Wisconsin
Froedtert Hospital, Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fate Therapeutics
Investigators
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Study Director: John Byon, MD, PhD Fate Therapeutics, Inc
Additional Information:
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Responsible Party: Fate Therapeutics
ClinicalTrials.gov Identifier: NCT05182073    
Other Study ID Numbers: FT576-101
First Posted: January 10, 2022    Key Record Dates
Last Update Posted: October 24, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fate Therapeutics:
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
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
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
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists