CD19-targeted CAR T Cells for Patients With Relapsed or Refractory in B-cell Acute Lymphoblastic Leukemia

NCT05727683 | Unknown Phase 1

• 1 other identifier: JWCAR029-006
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, open-label, single-arm study conducted in China to evaluate the safety, tolerability, PK, and determine the recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD) (if applicable) of JWCAR029 in pediatric and young adult subjects with r/r B-ALL.

Conditions

Acute Lymphocytic Leukemia

Keywords

JWCAR029; Relapsed/Refractory; Pediatric and young adults

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

  Dose limiting toxicity (DLT) is an AE that meets the following criteria and occurs within 28 days of JWCAR029 infusion.AE is graded according to CTCAE version 5.0, CRS is graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus CRS grading criteria, and neurotoxicity is graded according to the ASTCT 2019 consensus ICANS grading criteria.

  Day 28 after JWCAR029 infusion

• The occurrence of adverse events

  These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard

  After JWCAR029 infusion for 2 year

Secondary Outcomes (2)

• Overall remission Rate

  After JWCAR029 infusion for 2 year

• MRD negative rate

  After JWCAR029 infusion for 2 year

Study Arms (1)

JWCAR029 Treatment

EXPERIMENTAL

A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before JWCAR029 infusion. Potential JWCAR029 doses: Dose level 1: 0.10×10\^6 CAR+ T cells/kg Dose level 2: 0.30×10\^6 CAR+ T cells/kg Dose level 3: 0.75×10\^6 CAR+ T cells/kg Dose level 4: 1.0×10\^6 CAR+ T cells/kg

Biological: CD19-targeted Chimeric Antigen Receptor (CAR) T Cells

Interventions

CD19-targeted Chimeric Antigen Receptor (CAR) T Cells BIOLOGICAL

Subjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (25 mg/m2/day for 3 days) plus cyclophosphamide IV (250 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JWCAR029 cells infusion. Phase 1 will evaluate up to 4 JWCAR029 cells dose levels.

Also known as: Fludarabine, Cyclophosphamide

JWCAR029 Treatment

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≤ 30 years and weight ≥10kg.
• Patients with r/r B-ALL, defined as morphological disease in the bone marrow(≥5% blasts) and either of the following:
• ≥2 BM relapse;
• Refractory defined as relapse if first remission\<12 months or not achieving a CR after 1 cycle of a standard induction chemotherapy regimen for relapsed leukemia;primary chemo-refractory as defined by not achieving a CR after 1 cycle of a conventional chemotherapy or 2 cycles of a standard induction chemotherapy regimen for relapsed leukemia;
• Any BM relapse after HSCT which must be ≥90 days from HSCT at the time of screening, and be required free from GVHD and ended from any immunosuppressive therapy ≥1 month at the time of screening;
• Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated.
• Note: Patients with MRD+ after bridging therapy will be allowed for treatment.
• Karnofsky (age ≥16 years) or Lansky (age \<16 years) performance status \>60.
• Adequate organ function.
• Vascular access is sufficient for leukocyte isolation.
• Expected survival time \> 3 months.
• Any non-hematological toxicity due to previous treatment, except for alopecia and peripheral neuropathy, must be restored to ≤ grade 1.
• Females of childbearing potential (all female subjects who are physiologically capable of becoming pregnant) must agree to use a highly effective method of contraception for 1 year following JWCAR029 infusion; male subjects whose partners are of childbearing potential must agree to use an effective barrier method of contraception for 1 year following JWCAR029 infusion.

You may not qualify if:

• leukemic CNS involvement with active CNS lesions and significant neurodegenerative manifestations, or subjects with CNS grade CNS-2/CNS-3 as assessed by NCCN guidelines (subjects rated CNS-2 due to puncture injury may be enrolled).
• existing or previous clinically significant CNS lesions such as epilepsy, epileptic seizures, paralysis, aphasia, cerebral edema, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, etc.
• Patients with genetic syndromes other than Down syndrome.
• Patients with Burkitt's lymphoma.
• History of malignancy other than B-ALL for at least 2 years prior to enrollment.
• Subject has HBV, HCV, HIV or syphilis infection at the time of screening.
• Subject has deep vein thrombosis (DVT) (cancer thrombosis or thrombosis) or pulmonary artery embolism (PE) or is on anticoagulation therapy for DVT or PE within 3 months prior to signing the informed consent form
• uncontrolled systemic fungal, bacterial, viral or other infections.
• Combination of active autoimmune diseases requiring immunosuppressive therapy.
• Acute or chronic graft-versus-host disease.
• History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease.
• Women who are pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to initiation of lymphocyte clearance chemotherapy.
• Previous treatment with CAR-T cells or other gene-modified T cells.
• Previous anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
• Relevant medications or treatments within a specified time frame.

Sponsors & Collaborators

• Shanghai Ming Ju Biotechnology Co., Ltd.: lead

Study Sites (1)

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

Automobiles; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Motor Vehicles; Transportation; Technology, Industry, and Agriculture; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Xiaofan Zhu, PhD

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaofan Zhu, PhD

CONTACT

+86 13752090418; xfzhu@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2023
• First Posted: February 14, 2023
• Study Start: April 28, 2022
• Primary Completion: October 31, 2023
• Study Completion: July 31, 2025
• Last Updated: February 14, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)