Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Transformed Indolent Non-Hodgkin's Lymphoma
Conditions
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.
Interventions
DRUGFT596
Dosing to be initiated at a dose no higher than highest tolerable dose in study FT596-101, intravenously
DRUGCyclophosphamide
750 mg/m\^2 intravenously
DRUGDoxorubicin
50 mg/m\^2 intravenously
DRUGVincristine
1.4 mg/m\^2 (maximum dose 2 mg) intravenously
DRUGPrednisone
100 mg orally
DRUGRituximab
375 mg/m\^2 intravenously
DRUGBendamustine
90 mg/m\^2 IV infusion
Sponsors
Fate Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will be assigned to one of 2 treatment regimens corresponding to different schedules (standard or alternate) of R-CHOP
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Investigator-assessed complete response (CR) | Up to 2 years | Proportion of subjects who achieve a complete response (CR) per Lugano 2014 classification |
| 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. |
| Overall survival (OS) | Up to 15 years | Time from first dose of study treatment to death from any cause |
| 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 |
Outcome results
None listed