FT596 in Combination With R-CHOP in Subjects With B-Cell Lymphoma
- Conditions
- Diffuse Large B Cell LymphomaTransformed Indolent Non-Hodgkin's LymphomaFollicular LymphomaMantle Cell LymphomaMarginal Zone Lymphoma
- Interventions
- Registration Number
- NCT05934097
- Lead Sponsor
- Fate Therapeutics
- 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.
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
-
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen B (FT596 in combination with alternate schedule R-CHOP) FT596 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 Regimen A (FT596 in combination with standard schedule R-CHOP) FT596 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. Regimen A (FT596 in combination with standard schedule R-CHOP) Cyclophosphamide 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. Regimen A (FT596 in combination with standard schedule R-CHOP) Vincristine 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. Regimen A (FT596 in combination with standard schedule R-CHOP) Doxorubicin 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. Regimen A (FT596 in combination with standard schedule R-CHOP) Prednisone 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. Regimen B (FT596 in combination with alternate schedule R-CHOP) Cyclophosphamide 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 Regimen A (FT596 in combination with standard schedule R-CHOP) Rituximab 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. Regimen A (FT596 in combination with standard schedule R-CHOP) Bendamustine 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. Regimen B (FT596 in combination with alternate schedule R-CHOP) Doxorubicin 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 Regimen B (FT596 in combination with alternate schedule R-CHOP) Vincristine 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 Regimen B (FT596 in combination with alternate schedule R-CHOP) Rituximab 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 Regimen B (FT596 in combination with alternate schedule R-CHOP) Prednisone 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 Regimen B (FT596 in combination with alternate schedule R-CHOP) Bendamustine 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
- Primary Outcome Measures
Name Time Method Nature of dose-limiting toxicities within each dose escalation cohort Day 21 Incidence 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
Name Time Method Investigator-assessed complete response (CR) Up to 2 years Proportion of subjects who achieve a 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 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 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.