Allogeneic NK T-Cells Expressing CD19 Specific CAR in B-Cell Malignancies
- Conditions
- B-cell LeukemiaDLBCL - Diffuse Large B Cell LymphomaALL, ChildhoodNHL, Relapsed, AdultB-cell LymphomaALL, Adult B CellCLL/SLL
- Interventions
- Genetic: KUR-502
- Registration Number
- NCT05487651
- Lead Sponsor
- Athenex, Inc.
- Brief Summary
This study is a multi-center study to evaluate the safety of KUR-502 in subjects with refractory/relapsed B-cell NHL or leukemia (ALL or CLL).
- Detailed Description
KUR-502 will be manufactured from leukapheresis products from healthy donors. Subjects will be enrolled into 2 parallel cohorts (Cohort A \[non-ALL\] and Cohort B \[ALL\]). Each cohort will undergo dose escalation independently.
Three (3) dose levels will be evaluated in the ANCHOR and ANCHOR2 studies combined (1×107/m2, 3×107/m2, 1×108/m2). Dose levels are defined based on the number of transduced KUR-502 cells. Body surface area (BSA) will be capped at 2.4 m2. Subjects will receive \<1×104 allogeneic T cells/kg at any dose level.
The MTD will be determined once dose escalation is completed, and all subjects are evaluable for DLT. If there is no DLT that determines an MTD, a maximum dose level will be declared. Dose escalation will stop when 6 subjects have been treated at the MTD or highest dose level.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 36
Not provided
Subjects who meet any of the following criteria will be excluded from this study:
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Females who are breastfeeding or pregnant at Screening (as documented by a positive urine or serum pregnancy test; may be performed by local laboratory).
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Females of childbearing potential who:
- Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) through the Day 365 visit or for 30 days after study drug discontinuation.
- Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from sexual activity through the Day 365 visit or for 30 days after study drug discontinuation.
- Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive through the Day 365 visit or for 30 days after study drug discontinuation.
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Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception through the Day 365 visit or for 30 days after study drug discontinuation). No sperm donation is allowed through the Day 365 visit or for 30 days after study drug discontinuation.
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Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks prior to the KUR-502 infusion.
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History of Grade 2 to 4 GvHD.
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History of hypersensitivity reactions to murine protein-containing products.
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Active infection with human immunodeficiency virus (HIV) or human T cell lymphotropic virus (HTLV).
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Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
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Uncontrolled active bacterial, fungal, or other viral infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B, ALL releapsed/refractory KUR-502 This cohort is for patients with relapsed or refractory B-cell ALL afer 2 or more lines of therapy. Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion. Genetic: CD19.CAR-aNKT cells Patients will be given the T-cell product by intravenous injection (into the vein through an IV line) at the assigned dose. Dose level 1: 1×107/m2. Dose level 2: 3×107/m2. Dose level 3: 1×108/m2). Drug: Cyclophosphamide: Lymphodepletion chemotherapy. Patients will receive 3 daily doses of cyclophosphamide (500mg/m2/day finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle) Other name: Cytoxan Drug Fludarabine Lymphodepletion chemotherapy. Patient will receive 3 daily dose of fludarabine (30mg/m2/day) finishing at least 24 hours before T-cell infusion. the drug will be given intravenously (through an IV needle) Cohort A, non-ALL relapsed/refractory KUR-502 These dose levels will be evaluated. Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by CD19.CAR-aNKT cell infusion. Genetic: CD19.CAR-aNKT cells Patients will be given the T-cell product by intravenous injection (into the vein through an IV line) at the assigned dose. Dose level 1: 1×107/m2. Dose level 2: 3×107/m2. Dose level 3: 1×108/m2). Drug: Cyclophosphamide: Lymphodepletion chemotherapy. Patients will receive 3 daily doses of cyclophosphamide (500mg/m2/day finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle) Other name: Cytoxan Drug Fludarabine Lymphodepletion chemotherapy. Patient will receive 3 daily dose of fludarabine (30mg/m2/day) finishing at least 24 hours before T-cell infusion. the drug will be given intravenously (through an IV needle) Other name: Fludara
- Primary Outcome Measures
Name Time Method Dose limiting toxicity (DLT) rate and grade of single dose of Kur-502 4 weeks post T cell infusion Incidence rate and the grade (severity) of dose-limiting toxicities (DLTs) based on adverse events (AEs) reported according to the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
University of California, San Francisco
🇺🇸San Francisco, California, United States
OHSU - Knight Cancer Center
🇺🇸Portland, Oregon, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States