FT516 in Subjects With Advanced Hematologic Malignancies

Sponsor

Fate Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04023071

Collaborator

(none)

234

Enrollment

Locations

Arms

234.9

Anticipated Duration (Months)

33.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1/1b dose-finding study of FT516 as monotherapy in acute myeloid leukemia (AML) and in combination with CD20 directed monoclonal antibodies in B-cell lymphoma. The study includes three stages: dose escalation, safety confirmation, and dose expansion.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia B-cell Lymphoma	Drug: FT516 Drug: Rituximab Drug: Obinutuzumab Drug: Cyclophosphamide Drug: Fludarabine Drug: IL-2 Drug: Bendamustine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

234 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of FT516 as Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination With Monoclonal Antibodies in Relapsed/Refractory B-Cell Lymphoma

Actual Study Start Date :

Oct 4, 2019

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

May 1, 2039

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FT516 Monotherapy FT516 monotherapy in adult subjects with r/r AML.	Drug: FT516 Experimental Interventional Therapy Drug: Cyclophosphamide Conditioning agent Drug: Fludarabine Conditioning agent Drug: IL-2 Biologic response modifier
Experimental: FT516 in Combination with Monoclonal Antibodies FT516 in combination with one of the following monoclonal antibodies in adult subjects with r/r B-cell lymphoma: rituximab or obinutuzumab.	Drug: FT516 Experimental Interventional Therapy Drug: Rituximab Monoclonal Antibody Other Names: Rituxan MabThera Drug: Obinutuzumab Monoclonal Antibody Other Names: Gazyva Drug: Cyclophosphamide Conditioning agent Drug: Fludarabine Conditioning agent Drug: IL-2 Biologic response modifier
Experimental: FT516 in Combination with Monoclonal Antibodies on an Extended-Dosing Schedule FT516 on an extended-dosing schedule in combination with one of the following monoclonal antibodies in adult subjects with r/r B-cell lymphoma: rituximab or obinutuzumab.	Drug: FT516 Experimental Interventional Therapy Drug: Rituximab Monoclonal Antibody Other Names: Rituxan MabThera Drug: Obinutuzumab Monoclonal Antibody Other Names: Gazyva Drug: Cyclophosphamide Conditioning agent Drug: Fludarabine Conditioning agent Drug: IL-2 Biologic response modifier
Experimental: FT516 in Combination with Monoclonal Antibodies following Bendamustine Conditioning Bendamustine conditioning followed by FT516 in combination with one of the following monoclonal antibodies in adult subjects with r/r B-cell lymphoma: rituximab or obinutuzumab.	Drug: FT516 Experimental Interventional Therapy Drug: Rituximab Monoclonal Antibody Other Names: Rituxan MabThera Drug: Obinutuzumab Monoclonal Antibody Other Names: Gazyva Drug: IL-2 Biologic response modifier Drug: Bendamustine Conditioning agent Other Names: Bendeka Treanda

Outcome Measures

Primary Outcome Measures

The incidence of subjects with Dose Limiting Toxicities within each dose level cohort. [Day 29]
Incidence, nature, and severity of AEs, of FT516 as monotherapy in r/r AML and in combination with rituximab or obinutuzumab in r/r B-cell lymphoma. [Up to 5 years]

Secondary Outcome Measures

Investigator-assessed anti-tumor activity of FT516 as monotherapy in r/r AML and in combination with rituximab or obinutuzumab in r/r B-cell lymphoma. [Cycle 2 Day 29]
FT516 pharmacokinetic data [Cycle 1 and Cycle 2 Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29, and Cycle 2 Day 43 and Cycle 2 Day 57.]
Percentage of donor DNA measured at each timepoint

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

KEY INCLUSION CRITERIA:

Diagnosis of the following:

Regimen A (FT516 monotherapy):

Primary Refractory AML
Relapsed AML defined as not in CR after 1 or more re-induction attempts; if >60 years of age, prior re-induction therapy is not required

Regimen B (FT516 + rituximab or obinutuzumab):

Histologically documented B-cell lymphoma expected to express CD20 who have relapsed after or failed to respond to at least on prior treatment regimen and for whom there is no available therapy expected to improve survival.

All subjects:

Provision of signed and dated informed consent form (ICF)
Age ≥18 years old
Stated willingness to comply with study procedures and duration
Presence of measurable disease

KEY EXCLUSION CRITERIA:

All subjects:

Females of reproductive potential who are pregnant or lactating, and males or females not willing to use a highly effective form of contraception from Screening through the end of the study
Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2
Evidence of insufficient organ function
Receipt of therapy within 2 weeks prior to Cycle 1 Day 1 or within five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Cycle 1 Day 1
Currently receiving or likely to require systemic immunosuppressive therapy
Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Cycle 1 Day 1, or ongoing requirement for systemic graft-versus-host therapy
Receipt of an allograft organ transplant
Known active central nervous system (CNS) involvement by malignancy.
Clinically significant cardiovascular disease
Clinically significant infections including: Known HIV infection; Known active Hepatitis B (HBV) or Hepatitis C (HCV) infection
Live vaccine <6 weeks prior to start of lympho-conditioning
Known allergy to human albumin and DMSO

Additional Exclusion Criteria for FT516 monotherapy Regimen: Diagnosis of promyelocytic leukemia with t(15:17) translocation

Additional Exclusion Criteria for FT516 plus monoclonal antibody Regimens: Diagnosis of Waldenstrom macroglobulinemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	UC San Diego	San Diego	California	United States	92037
3	University of Colorado, Denver	Denver	Colorado	United States	80045
4	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
5	UT Southwestern	Dallas	Texas	United States	75390
6	MD Anderson Cancer Center	Houston	Texas	United States	77030
7	Swedish Cancer Institute	Seattle	Washington	United States	98104