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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Diffuse Large B Cell Lymphoma; Transformed Indolent Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: FT596; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab; Drug: Bendamustine

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 Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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; Ruxience; Truxima; Drug: Bendamustine; 90 mg/m^2 IV infusion; Other Names: Treanda; Bendeka
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; Ruxience; Truxima; Drug: Bendamustine; 90 mg/m^2 IV infusion; Other Names: Treanda; Bendeka

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from first dose of study treatment to death from any cause	Up to 15 years
Investigator-assessed complete response (CR)	Proportion of subjects who achieve a complete response (CR) per Lugano 2014 classification	Up to 2 years
Investigator-assessed objective-response rate (ORR)	Proportion of subjects who achieve a partial response (PR) or complete response (CR) per Lugano 2014 classification	Up to 2 years
Investigator-assessed duration of response (DOR)	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	Up to 15 years
Investigator-assessed duration of complete response (DoCR)	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	Up to 15 years
Progression-free survival (PFS)	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	Up to 15 years
Area Under the Plasma Concentration Time Curve (AUC) of FT596	Assessed by the detection of FT596 in peripheral blood following FT596 administration.	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
Maximum Plasma Concentration (Cmax) of FT596	Assessed by the detection of FT596 in peripheral blood following FT596 administration.	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

Collaborators and Investigators

• Sponsor: Fate Therapeutics
• Investigators: Study Director: Fate Trial Disclosure, Fate Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2039

Study Registration Dates

• First Submitted: April 30, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Bendamustine Hydrochloride; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: FT596-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No