Clinical trial NCT04245722: FT596 as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma, B-Cell
Chronic Lymphocytic Leukemia
Keywords: Lymphoma
Leukemia
Lead sponsor: Fate Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-01-29
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose-limiting toxicities within each dose level cohort
timeFrame: Day 29
measure: Nature of dose-limiting toxicities within each dose level cohort
timeFrame: Day 29
measure: 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
timeFrame: Up to 15 years
Secondary outcomes:
measure: Investigator-assessed objective-response rate (ORR)
timeFrame: From baseline tumor assessment up to approximately 2 years after last dose of FT596
measure: Investigator-assessed duration of objective response (DOR)
timeFrame: Up to 15 years
measure: Investigator-assessed duration of complete response (DoCR)
timeFrame: Up to 15 years
measure: Progression-free survival (PFS)
timeFrame: Up to 15 years
measure: Overall survival (OS), defined as the time from first dose of lympho-conditioning to death from any cause.
timeFrame: Up to 15 years
measure: 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
timeFrame: Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (Tennessee Oncology)
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: SCRI-TTI
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Fate Therapeutics
name: Fate Trial Disclosure
role: STUDY_DIRECTOR
References:
citation: 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.