FT819 in Subjects With B-cell Malignancies

Sponsor

Fate Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04629729

Collaborator

(none)

297

Enrollment

Locations

Arms

218.2

Anticipated Duration (Months)

37.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase I dose-finding study of FT819 as monotherapy and in combination with IL-2 in subjects with relapsed/refractory B-cell Lymphoma, Chronic Lymphocytic Leukemia and Precursor B-cell Acute Lymphoblastic Leukemia. 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
Lymphoma, B-Cell Chronic Lymphocytic Leukemia Precursor B-Cell Acute Lymphoblastic Leukemia	Drug: FT819 Drug: Cyclophosphamide Drug: Fludarabine Drug: IL-2	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

297 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of FT819 in Subjects With B-cell Malignancies

Actual Study Start Date :

Jul 26, 2021

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2039

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FT819 Single-Dose Monotherapy, B-Cell Lymphoma FT819 single-dose monotherapy in adult subjects with r/r B-cell Lymphoma	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent
Experimental: FT819 Single-Dose in Combination with IL-2, B-Cell Lymphoma FT819 single-dose in combination with IL-2 in adult subjects with r/r B-cell Lymphoma	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent Drug: IL-2 Biologic response modifier Other Names: Interleukin-2
Experimental: FT819 Step Fractionated Monotherapy, B-Cell Lymphoma FT819 monotherapy administered as step-fractionated dosing in adult subjects with r/r B-cell Lymphoma	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent
Experimental: FT819 Single-Dose Monotherapy, CLL FT819 single-dose monotherapy in adult subjects with r/r CLL	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent
Experimental: FT819 Single-Dose in Combination with IL-2, CLL FT819 single-dose in combination with IL-2 in adult subjects with r/r CLL	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent Drug: IL-2 Biologic response modifier Other Names: Interleukin-2
Experimental: FT819 Step Fractionated Monotherapy, CLL FT819 monotherapy administered as step-fractionated dosing in adult subjects with r/r CLL	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent
Experimental: FT819 Single-Dose Monotherapy, B-ALL FT819 single-dose monotherapy in adult subjects with r/r B-ALL	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent
Experimental: FT819 Single-Dose in Combination with IL-2, B-ALL FT819 single-dose in combination with IL-2 in adult subjects with r/r B-ALL	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent Drug: IL-2 Biologic response modifier Other Names: Interleukin-2
Experimental: FT819 Step Fractionated Monotherapy, B-ALL FT819 monotherapy administered as step-fractionated dosing in adult subjects with r/r B-ALL	Drug: FT819 Experimental Interventional Therapy Drug: Cyclophosphamide Lympho-conditioning agent Drug: Fludarabine Lympho-conditioning agent

Outcome Measures

Primary Outcome Measures

Incidence and nature of dose-limiting toxicities within each dose level cohort [Day 29]
Incidence, nature, and severity of adverse events (AEs) of FT819 as monotherapy and in combination with IL-2 in r/r B-cell lymphoma, r/r chronic lymphocytic leukemia, and r/r precursor B-cell acute lymphoblastic leukemia [Up to 15 years]

Secondary Outcome Measures

Investigator-assessed objective-response rate (ORR) [From baseline assessment up to approximately 2 years after last dose of FT819]
For BCL and CLL Only: Investigator-assessed duration of objective response (DOR) [Up to 15 years]
For BCL and CLL Only: Investigator-assessed duration of complete response (DoCR) [Up to 15 years]
For BCL and CLL Only: Progression-free survival (PFS) [Up to 15 years]
Overall survival (OS) [Up to 15 years]
Determination of the pharmacokinetics of FT819 cells in peripheral blood. [Study Days 1, 2, 3, 4, 5, 6, 8, 11, 15, 18, 22, 25, and 29]
The PK of FT819 in peripheral blood will be reported as the relative percentage of product (FT819) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points
For B-ALL Only: Investigator-assessed relapse-free survival (RFS) [Up to 15 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Diagnosis of B-cell lymphoma, CLL or B-ALL as described below:

B-Cell Lymphoma:

Histologically documented lymphomas expected to express CD19
Relapsed/refractory disease following at least 2 prior lines of multi-agent immunochemotherapy

Chronic Lymphocytic Leukemia (CLL):

Diagnosis of CLL per iwCLL guidelines
Relapsed/refractory disease following at least two prior systemic treatment regimens

Precursor B-cell Acute Lymphocytic Leukemia (B-ALL):

Diagnosis of B-ALL by flow cytometry, bone marrow histology, and/or cytogenetics
Relapsed/refractory disease after at least 2 cycles of standard multiagent induction chemotherapy. For subjects with Philadelphia-chromosome positive (Ph+) disease, failure or intolerance to a tyrosine kinase inhibitor therapy-containing regimen

ALL SUBJECTS:

Capable of giving signed informed consent
Age ≥ 18 years old
Stated willingness to comply with study procedures and duration
Contraceptive use for women and men as defined in the protocol

Key Exclusion Criteria:

ALL SUBJECTS:

Females who are pregnant or breastfeeding
Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2
Body weight <50 kg
Evidence of insufficient organ function
Receipt of therapy 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
Currently receiving or likely to require systemic immunosuppressive therapy
Ongoing requirement for systemic GvHD therapy following prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T
Receipt of an allograft organ transplant
Known active central nervous system (CNS) involvement by malignancy
Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
Clinically significant cardiovascular disease
Positive serologic test results for HIV infection
Positive serologic and polymerase chain reaction (PCR) test results for Hepatitis B (HBV) infection
Positive serologic and PCR test results for Hepatitis C (HCV) infection
Live vaccine <6 weeks prior to start of lympho-conditioning
Known allergy to albumin (human) or DMSO

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of Iowa	Iowa City	Iowa	United States	52242
3	The University of Kansas Medical Center	Westwood	Kansas	United States	66205
4	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
6	Oregon Health & Sciences University	Portland	Oregon	United States	97239
7	MD Anderson Cancer Center	Houston	Texas	United States	77030
8	University of Wisconsin-Madison	Madison	Wisconsin	United States	53705