FT522 With Rituximab in Relapsed/Refractory B-Cell Lymphoma (FT522-101)

Sponsor

Fate Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05950334

Collaborator

(none)

322

Enrollment

Arms

196

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a phase 1 study of FT522 administered with rituximab in participants with relapsed/refractory B-cell lymphoma (R/R BCL). The primary objectives of the study are to evaluate the safety and tolerability of FT522 in combination with rituximab, and to determine the recommended phase 2 dose (RP2D) of FT522 in combination with rituximab; each objective will be assessed with or without conditioning chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory B-Cell Lymphoma	Drug: FT522 Drug: Rituximab Drug: Cyclophosphamide Drug: Fludarabine Drug: Bendamustine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

322 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Participants will be enrolled first into a dose-escalation stage, followed by a dose optimization stage, and a dose-expansion stage.Participants will be enrolled first into a dose-escalation stage, followed by a dose optimization stage, and a dose-expansion stage.

Masking:

None (Open Label)

Masking Description:

The initial dose escalation stage of the study is nonrandomized; the dose optimization stage is randomized; the dose expansion stage is nonrandomized.

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of FT522 in Combination With Rituximab in Participants With Relapsed/Refractory B-Cell Lymphoma

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2039

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen A Participants receive FT522 in combination with rituximab (or a rituximab biosimilar approved by a local health authority) with chemotherapy.	Drug: FT522 FT522 drug product is administered as an intravenous infusion on Days 1, 4 and 8 of a treatment cycle. Drug: Rituximab Rituximab will be administered as an IV infusion on Day -4 of the treatment cycle. Other Names: RITUXAN TRUXIMA RUXIENCE RIABNI Drug: Cyclophosphamide Cyclophosphamide will be administered as an IV infusion at a dose of 500 mg/m^2 on Day -5, Day -4, and Day -3 of the treatment cycle. Drug: Fludarabine Fludarabine will be administered as an IV infusion at a dose of 30 mg/m^2 on Day -5, Day -4, and Day -3 of the treatment cycle. Drug: Bendamustine Bendamustine will be administered as an IV infusion at a dose of 90 mg/m^2 on Day -5 and Day -4 of the treatment cycle. Bendamustine may be administered as an alternative to cyclophosphamide/fludarabine.
Experimental: Regimen B Participants receive FT522 in combination with rituximab (or a rituximab biosimilar approved by a local health authority) without chemotherapy.	Drug: FT522 FT522 drug product is administered as an intravenous infusion on Days 1, 4 and 8 of a treatment cycle. Drug: Rituximab Rituximab will be administered as an IV infusion on Day -4 of the treatment cycle. Other Names: RITUXAN TRUXIMA RUXIENCE RIABNI

Arm

Intervention/Treatment

Experimental: Regimen A

Participants receive FT522 in combination with rituximab (or a rituximab biosimilar approved by a local health authority) with chemotherapy.

Drug: FT522

FT522 drug product is administered as an intravenous infusion on Days 1, 4 and 8 of a treatment cycle.

Drug: Rituximab

Rituximab will be administered as an IV infusion on Day -4 of the treatment cycle.

Other Names:

RITUXAN

TRUXIMA

RUXIENCE

RIABNI

Drug: Cyclophosphamide

Cyclophosphamide will be administered as an IV infusion at a dose of 500 mg/m^2 on Day -5, Day -4, and Day -3 of the treatment cycle.

Drug: Fludarabine

Fludarabine will be administered as an IV infusion at a dose of 30 mg/m^2 on Day -5, Day -4, and Day -3 of the treatment cycle.

Drug: Bendamustine

Bendamustine will be administered as an IV infusion at a dose of 90 mg/m^2 on Day -5 and Day -4 of the treatment cycle. Bendamustine may be administered as an alternative to cyclophosphamide/fludarabine.

Experimental: Regimen B

Participants receive FT522 in combination with rituximab (or a rituximab biosimilar approved by a local health authority) without chemotherapy.

Drug: FT522

FT522 drug product is administered as an intravenous infusion on Days 1, 4 and 8 of a treatment cycle.

Drug: Rituximab

Rituximab will be administered as an IV infusion on Day -4 of the treatment cycle.

Other Names:

RITUXAN

TRUXIMA

RUXIENCE

RIABNI

Outcome Measures

Primary Outcome Measures

Number of participants with dose limiting toxicities (DLTs) [From Day 1 through Day 29 of Cycle 1]
The number of participants experiencing ≥1 DLT will be reported.
Severity of DLTs [From Day 1 through Day 29 of Cycle 1]
The severity of DLTs will be determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, v5.0).

Secondary Outcome Measures

Overall Response Rate (ORR) [Up to approximately 24 months]
Participants will be classified into the following tumor response categories: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE) according to the Lugano 2014 criteria. The best overall response (BOR) will be summarized for the efficacy evaluable population. ORR is defined as the percentage of participants who achieve a PR or better during the study prior to any subsequent off-protocol anti-cancer therapy.
Duration of Response (DOR) [Up to approximately 18 months]
The DOR is defined as the time from first objective response to disease progression or death from any cause.
Duration of Complete Response (DOCR) [Up to approximately 18 months]
The DOCR is defined as the time from first CR to disease progression or death from any cause.
Progression-Free Survival (PFS) [Up to approximately 18 months]
PFS is defined as the time from first study intervention to progressive disease or death from any cause.
Overall Survival (OS) [Up to approximately 18 months]
OS is defined as the time from first dose of study intervention to death from any cause.
Area Under the Plasma-Concentration Time Curve (AUC) of FT522 [Cycle 1, Up to Day 29]
The plasma AUC of FT522 will be reported.
Maximum Plasma Concentration (Cmax) of FT522 [Cycle 1, Up to Day 29]
The plasma Cmax of FT522 will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of B-cell lymphoma (BCL) as: histologically documented lymphomas expected to express CD19 and CD20, including Grades 1 to 3B follicular lymphoma (FL), transformed indolent non-Hodgkin lymphoma (tNHL), diffuse large B-cell lymphoma (DLBCL) [not otherwise specified], high-grade BCL, and primary mediastinal BCL; R/R disease following at least 1 prior systemic regimen containing an anti-CD20 monoclonal antibody (mAb) for which the participant has no available curative treatment options; evaluable F-fluorodeoxyglucose (FDG)-avid disease, or measurable disease defined by at least one bi dimensionally measurable lesion
Male participants and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception

Exclusion Criteria:

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 any biological therapy, chemotherapy (except for rituximab), or any investigational therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or localized radiation therapy to a target lesion within 14 days prior to Day 1
Currently receiving or likely to require systemic immunosuppressive therapy, e.g., prednisone >5 mg daily, for any reason from Day -5 to Day 29, with the exception of corticosteroids as a pre medication required for conditioning chemotherapy or rituximab
Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic chimeric antigen receptor (CAR) T-cell therapy within 6 months of Day 1, or ongoing requirement for systemic graft-versus-host disease (GvHD) therapy
Receipt of an allograft organ transplant
Non-malignant central nervous system (CNS) disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
Clinically significant cardiovascular disease
Clinically significant infections
Receipt of a live vaccine <6 weeks prior to start of study intervention
Known allergy to human albumin or DMSO
Any medical condition or clinical laboratory abnormality that per investigator or medical monitor judgement, precludes safe participation in and completion of the study, or that could affect compliance with protocol conduct or interpretation of results