FT596 as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase I, Open-Label, Multicenter Study of FT596 as a Monotherapy and in Combination With Rituximab or Obinutuzumab in Subjects With Relapsed/Refractory B-cell Lymphoma and Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04245722
• Other study ID #: FT596-101
• Status: Terminated
• Phase: Phase 1
• Start date: March 19, 2020
• Est. completion date: September 27, 2023

Study information

• Verified date: October 2023
• Source: Fate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase I dose-finding study of FT596 as monotherapy and in combination with Rituximab or Obinutuzumab in subjects with relapsed/refractory B-cell Lymphoma or Chronic Lymphocytic Leukemia. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 98
• Est. completion date: September 27, 2023
• Est. primary completion date: September 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

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

B-Cell Lymphoma:

• Histologically documented lymphomas expected to express CD19 and CD20

• Relapsed/refractory disease following prior systemic immunochemotherapy regimen

Chronic Lymphocytic Leukemia (CLL):

• Diagnosis of CLL per iwCLL guidelines

• Relapsed/refractory disease following at least two prior systemic treatment regimens

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 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

• Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic GvHD therapy

• 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

• 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 albumin (human) or DMSO

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• FT596
Experimental Interventional Therapy
• Cyclophosphamide
Lympho-conditioning agent
• Fludarabine
Lympho-conditioning agent
• Rituximab
Monoclonal Antibody
• Obinutuzumab
Monoclonal Antibody
• Bendamustine
Conditioning agent

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute (Tennessee Oncology)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone Health	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	SCRI-TTI	San Antonio	Texas
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. Cell Stem Cell. 2018 Aug 2;23(2):181-192.e5. doi: 10.1016/j.stem.2018.06.002. Epub 2018 Jun 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities within each dose level cohort		Day 29
Primary	Nature of dose-limiting toxicities within each dose level cohort		Day 29
Primary	Incidence, nature, and severity of adverse events (AEs) of FT596 as monotherapy and in combination with rituximab or obinutuzumab in r/r B-cell lymphomas and r/r chronic lymphocytic leukemia, with severity determined according to NCI CTCAE, v5.0		Up to 15 years
Secondary	Investigator-assessed objective-response rate (ORR)	Proportion of subjects who achieve a partial response (PR) or complete response (CR) per Lugano 2014 classification for lymphomas, a partial remission (PR) or complete remission (CR) per revised iwCLL guidelines for CLL.	From baseline tumor assessment up to approximately 2 years after last dose of FT596
Secondary	Investigator-assessed duration of objective response (DOR)	Defined as the duration from the first occurrence of a documented objective response (DOR) until the time of disease progression or relapse, or death from any cause, whichever occurs first, per Lugano 2014 classification for lymphomas or revised iwCLL guidelines for CLL.	Up to 15 years
Secondary	Investigator-assessed duration of complete response (DoCR)	Defined as the duration from the first occurrence of a documented complete response (CR) per Lugano 2014 classification for lymphomas or complete remission (CR) per revised iwCLL guidelines for CLL, until the time of disease progression or relapse, or death from any cause, whichever occurs first.	Up to 15 years
Secondary	Progression-free survival (PFS)	Defined as the time from from first dose of lympho-conditioning to progressive disease (PD), or to the day of death for any reason, whichever occurs earlier, based on Lugano 2014 classification for lymphomas or revised iwCLL guidelines for CLL	Up to 15 years
Secondary	Overall survival (OS), defined as the time from first dose of lympho-conditioning to death from any cause.		Up to 15 years
Secondary	The pharmacokinetics of FT596 in peripheral blood will be reported as the relative percentage of product (FT596) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points		Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29