FT596 in Combination With R-CHOP in Subjects With B-Cell Lymphoma

Sponsor

Fate Therapeutics (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT05934097

Collaborator

(none)

Enrollment

Arms

197

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase I study of FT596 in combination with two different schedules (standard or alternate) of R-CHOP in subjects with B-cell lymphoma who are previously untreated or have received no more than one prior line of treatment. The study will consist of a dose-escalation stage followed by a dose-expansion stage.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma Transformed Indolent Non-Hodgkin's Lymphoma Follicular Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma	Drug: FT596 Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Rituximab Drug: Bendamustine	Phase 1

Detailed Description

This is a Phase I study of FT596 in combination with 2 different schedules (standard or alternate) of R-CHOP in subjects with B-cell lymphoma who are previously untreated or have received no more than one prior line of treatment.

The study will evaluate both the clinical benefit of FT596 when combined with R-CHOP given on a standard or alternate schedule.

Subjects will be enrolled in two stages: a dose-escalation stage and a dose-expansion stage. After safety and tolerability have been assessed to define the maximum tolerated dose (MTD) (or the maximum assessed dose [MAD] in the absence of dose limiting toxicities [DLTs] defining the MTD) in the dose-escalation stage, the dose-expansion stage will further evaluate the safety and activity of FT596 in combination.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be assigned to one of 2 treatment regimens corresponding to different schedules (standard or alternate) of R-CHOPSubjects will be assigned to one of 2 treatment regimens corresponding to different schedules (standard or alternate) of R-CHOP

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b, Open-Label, Multicenter Study of FT596 in Combination With R-CHOP in Subjects With B-Cell Lymphoma

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

May 1, 2039

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen A (FT596 in combination with standard schedule R-CHOP) FT596 in combination with standard schedule R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on Day 1; prednisone on Days 1-5; and FT596 on Day 8) for a total of six 21-day cycles.	Drug: FT596 Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously Drug: Cyclophosphamide 750 mg/m^2 intravenously Drug: Doxorubicin 50 mg/m^2 intravenously Drug: Vincristine 1.4 mg/m^2 (maximum dose 2 mg) intravenously Drug: Prednisone 100 mg orally Drug: Rituximab 375 mg/m^2 intravenously Other Names: Rituxan Truxima Ruxience Drug: Bendamustine 90 mg/m^2 IV infusion Other Names: Bendeka Treanda
Experimental: Regimen B (FT596 in combination with alternate schedule R-CHOP) FT596 in combination with alternate schedule R-CHOP (prednisone on Days 1-5; rituximab, cyclophosphamide, doxorubicin, and vincristine on Day 5; and FT596 on Day 8) for a total of six 21-day cycles	Drug: FT596 Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously Drug: Cyclophosphamide 750 mg/m^2 intravenously Drug: Doxorubicin 50 mg/m^2 intravenously Drug: Vincristine 1.4 mg/m^2 (maximum dose 2 mg) intravenously Drug: Prednisone 100 mg orally Drug: Rituximab 375 mg/m^2 intravenously Other Names: Rituxan Truxima Ruxience Drug: Bendamustine 90 mg/m^2 IV infusion Other Names: Bendeka Treanda

Arm

Intervention/Treatment

Experimental: Regimen A (FT596 in combination with standard schedule R-CHOP)

FT596 in combination with standard schedule R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on Day 1; prednisone on Days 1-5; and FT596 on Day 8) for a total of six 21-day cycles.

Drug: FT596

Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously

Drug: Cyclophosphamide

750 mg/m^2 intravenously

Drug: Doxorubicin

50 mg/m^2 intravenously

Drug: Vincristine

1.4 mg/m^2 (maximum dose 2 mg) intravenously

Drug: Prednisone

100 mg orally

Drug: Rituximab

375 mg/m^2 intravenously

Other Names:

Rituxan

Truxima

Ruxience

Drug: Bendamustine

90 mg/m^2 IV infusion

Other Names:

Bendeka

Treanda

Experimental: Regimen B (FT596 in combination with alternate schedule R-CHOP)

FT596 in combination with alternate schedule R-CHOP (prednisone on Days 1-5; rituximab, cyclophosphamide, doxorubicin, and vincristine on Day 5; and FT596 on Day 8) for a total of six 21-day cycles

Drug: FT596

Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously

Drug: Cyclophosphamide

750 mg/m^2 intravenously

Drug: Doxorubicin

50 mg/m^2 intravenously

Drug: Vincristine

1.4 mg/m^2 (maximum dose 2 mg) intravenously

Drug: Prednisone

100 mg orally

Drug: Rituximab

375 mg/m^2 intravenously

Other Names:

Rituxan

Truxima

Ruxience

Drug: Bendamustine

90 mg/m^2 IV infusion

Other Names:

Bendeka

Treanda

Outcome Measures

Primary Outcome Measures

Incidence of dose-limiting toxicities within each dose escalation cohort [Day 21]
Nature of dose-limiting toxicities within each dose escalation cohort [Day 21]
Incidence, nature, and severity of adverse events (AEs) of FT596 in combination with R-CHOP in B-cell lymphoma previously untreated or no more than one previous line of therapy with severity determined according to NCI CTCAE, v5.0 [Up to 5 years]

Secondary Outcome Measures

Investigator-assessed complete response (CR) [Up to 2 years]
Proportion of subjects who achieve a complete response (CR) per Lugano 2014 classification
Investigator-assessed objective-response rate (ORR) [Up to 2 years]
Proportion of subjects who achieve a partial response (PR) or complete response (CR) per Lugano 2014 classification
Investigator-assessed duration of response (DOR) [Up to 15 years]
Duration from the first occurrence of a documented objective response until the time of disease progression or relapse, or death from any cause, whichever occurs first, per Lugano 2014 classification
Investigator-assessed duration of complete response (DoCR) [Up to 15 years]
Duration from the first occurrence of a documented complete response (CR), per Lugano 2014 classification until the time of disease progression or relapse, or death from any cause, whichever occurs first
Progression-free survival (PFS) [Up to 15 years]
Time from first dose of study treatment to progressive disease (PD), or to the day of death for any reason, whichever occurs earlier, based on Lugano 2014 classification
Overall survival (OS) [Up to 15 years]
Time from first dose of study treatment to death from any cause
Area Under the Plasma Concentration Time Curve (AUC) of FT596 [Cycles 1-6 (each cycle is 28 days): Days 1,8,11,15,18; and Post-Treatment Week 1, Week 2, Week 4, and Week 8]
Assessed by the detection of FT596 in peripheral blood following FT596 administration.
Maximum Plasma Concentration (Cmax) of FT596 [Cycles 1-6 (each cycle is 28 days): Days 1,8,11,15,18; and Post-Treatment Week 1, Week 2, Week 4, and Week 8]
Assessed by the detection of FT596 in peripheral blood following FT596 administration.

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 (BCL) as described below:
Histologically documented BCL
Previously untreated or no more than one prior systemic therapy for BCL
At least one bi-dimensionally measurable lesion
Subjects with >1 measurable lesion agreement to undergo a biopsy
Capable of giving signed informed consent
Age ≥ 18 years old
Stated willingness to comply with study procedures through study duration
Contraception use for women and men as defined in the protocol
Negative serum pregnancy test within 7 days of treatment for women

Key Exclusion Criteria:

Prior anthracycline therapy
Females who are pregnant or breastfeeding
Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2
Evidence of insufficient organ function
Currently receiving or likely to receive systemic immunosuppressive therapy
Receipt of 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 HIV test
Positive Hepatitis B (HBV) or Hepatitis C (HCV) test
Live vaccine <6 weeks prior to start of conditioning
Allergy to human albumin or dimethyl sulfoxide (DMSO)