Allogeneic NK T-Cells Expressing CD19 Specific CAR in B-Cell Malignancies

NCT05487651 | Unknown Phase 1 FDA Drug

• 1 other identifier: ATX-K502-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

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).

Conditions

NHL, Relapsed, Adult; B-cell Lymphoma; B-cell Leukemia; DLBCL - Diffuse Large B Cell Lymphoma; ALL, Adult B Cell; ALL, Childhood; CLL/SLL

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) rate and grade of single dose of Kur-502

  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

  4 weeks post T cell infusion

Study Arms (2)

Cohort A, non-ALL relapsed/refractory

EXPERIMENTAL

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

Genetic: KUR-502

Cohort B, ALL releapsed/refractory

EXPERIMENTAL

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)

Genetic: KUR-502

Interventions

KUR-502 GENETIC

KUR-502 (CD19.CAR-aNKT cells) consists of transduced allogeneic natural killer T cells (aNKT) genetically modified with additional features to enhance their anti-tumor activity against CD19+ B-cell malignancies. Following intravenous (IV) infusion, the product is expected to kill CD19+ tumor cells by direct interaction with the chimeric antigen receptor (CAR), and activation of the NKT cells to kill tumor through their innate cell killing.

Also known as: CD19.CAR-aNKT cells

Cohort A, non-ALL relapsed/refractory; Cohort B, ALL releapsed/refractory

Eligibility Criteria

• Age: 3 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be included in this study:
• Signed written informed consent.
• Diagnosis of CD19+ B-cell lymphoma or leukemia (ALL or CLL).
• Subjects who previously received CD19-directed therapy must have biopsy or flow cytometry-confirmed CD19+ tumor following the CD19-directed therapy; may be performed by local laboratory.
• The disease is:
• Cohort A (non-ALL subjects):
• Relapsed or refractory after ≥2 lines of therapy, including a CD20 antibody, if an indolent lymphoma.
• Relapsed or refractory after ≥2 lines of therapy, including ibrutinib and venetoclax, if CLL.
• Relapsed or refractory after ≥2 lines of therapy, including a CD20 antibody and an anthracycline, and the subject is ineligible for autologous stem cell transplantation, if an aggressive or highly aggressive lymphoma.
• Ineligibility for autologous stem cell transplantation includes non-responsive disease after salvage therapy and failure to mobilize stem cells for transplant.
• Cohort B (ALL subjects):
• Relapsed or refractory after ≥2 lines of therapy.
• Measurable disease by current criteria (Lugano criteria for lymphomas, IWG criteria for CLL, and detectable disease for ALL).
• Age 3 to 75 years; subjects \<18 years old will not be enrolled as the first subject on any dose level.
• BSA ≤2.4 m2.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Females who are breastfeeding or pregnant at Screening (as documented by a positive urine or serum pregnancy test; may be performed by local laboratory).
• 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.
• 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.
• Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks prior to the KUR-502 infusion.
• History of Grade 2 to 4 GvHD.
• History of hypersensitivity reactions to murine protein-containing products.
• Active infection with human immunodeficiency virus (HIV) or human T cell lymphotropic virus (HTLV).
• Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Uncontrolled active bacterial, fungal, or other viral infection.

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

OHSU - Knight Cancer Center

Portland, Oregon, 97239, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence; Lymphoma, B-Cell; Leukemia, B-Cell; Dendritic Cell Sarcoma, Interdigitating; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Histiocytic Disorders, Malignant; Histiocytosis

Study Officials

• Carlos Ramos, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dan Lang, MD, PhD

CONTACT

716-970-4187; dlang@athenex.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 dose escalation

Study Record Dates

• First Submitted: August 1, 2022
• First Posted: August 4, 2022
• Study Start: October 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: May 18, 2023

Record last verified: 2023-05

Locations

US (3)