Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10- 19) in the Treatment of r/r B-ALL Clinical Research

Sponsor
Anhui Provincial Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05747157
Collaborator
Leman Biotech Co., Ltd (Other)
18
1
1
26
0.7

Study Details

Study Description

Brief Summary

A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia

Condition or Disease Intervention/Treatment Phase
  • Drug: Metabolically Armed CD19 CAR-T cells
Early Phase 1

Detailed Description

This is a single arm , open-label study. This study is indicated for relapsed and/or refractory CD19+ B-cell Acute Lymphoblastic Leukemia . The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products.

  1. Main research objectives:

To evaluate the safety and efficacy of metabolically armed CD19 CAR-T Cells in the treatment of r/r B-ALL.

  1. Secondary research objectives:
  1. To evaluate the pharmacokinetic (PK) and pharmacodynamics(PD) characteristics of metabolically armed CD19 CAR-T Cells after infusion.

  2. To evaluate tumor remission after infusion of metabolically armed CD19 CAR-T Cells.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10- 19) in the Treatment of r/r B-ALL Clinical Research
Anticipated Study Start Date :
Mar 17, 2023
Anticipated Primary Completion Date :
Feb 1, 2025
Anticipated Study Completion Date :
May 15, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Administration of Metabolically Armed CD19 CAR-T cells

Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. A dose of metabolically armed CD19 CAR-T cells will be infused on day 0.

Drug: Metabolically Armed CD19 CAR-T cells
Each subject receive metabolically armed CD19 CAR-T cells by intravenous infusion.
Other Names:
  • Meta10-19
  • Outcome Measures

    Primary Outcome Measures

    1. MTD [MTD will be determined based on DLTs observed during the first 28 days of study treatment]

      Determine the Maximal Tolerable Dose(MTD)

    2. Objective response rate (ORR) [Within 3 months following infusion of Meta10- 19]

      Measure Tumor response rate (including CR and PR)

    Secondary Outcome Measures

    1. Pharmacokinetics [Up to 12 months after CAR-T treatment]

      The number of CAR-T cells in peripheral blood was measured to evaluate the persistence of CAR-T cells

    2. Pharmacodynamics [Up to 28 days after infusion]

      Peak level of cytokines in peripheral blood

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. The patient or his/her guardian voluntarily signed the informed consent;

    2. Adult Patients with relapsed and refractory B-cell Acute Lymphoblastic Leukemia.

    Definition of relapsed or refractory B-ALL (meeting one of the following conditions):
    1. 2 or more relapses;

    2. Bone marrow relapsed after allo-HSCT and prepared to infuse Meta10-19 more than 6 months after allo-HSCT ;

    3. CR not achieved after standardized chemotherapy;

    4. Philadelphia-chromosome-positive (Ph+) patients who are ineffective or intolerant to first- and second-generation tyrosine kinase inhibitor (TKI) treatments, or who have contraindications to tyrosine kinase inhibitors;

    5. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is ≥ 5%

    6. CD19 expression was positive by biopsy or flow cytometry (accept the results of this peripheral blood mononuclear cells collection or previous Class A tertiary hospital before this peripheral blood collection);

    7. Expected survival time greater than 12 weeks

    8. The baseline ECOG score was 0 or 1;

    9. Organ function:

    10. Kidney function:

    Serum creatinine ≤1.5 times ULN, or; The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/min/1.73m2;[eGFR=186×(age)-0.203×SCr-1.154(mg/dl),for females, the result was ×0.742];

    1. Liver function: ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-.Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included.

    2. Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment.

    3. Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45%;

    4. Patients using the following drugs must meet the following conditions:

    5. Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, hydrocortisone or its equivalent < 6-12mg/mm2/ day;

    6. Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks before the informed consent is signed;

    7. Anti-proliferative therapy other than preconditioning chemotherapy is discontinued within 2 weeks prior to Meta10-19 infusion;

    8. Treatment for CNS disease must be stopped 1 week before Meta10-19 infusion (e.g., intrathecal methotrexate)

    9. The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or less, such as hair loss, which the researchers have determined is not recoverable in a short period of time) is suitable for pretreatment chemotherapy and CAR-T cell therapy;

    10. Women of childbearing age and all male patients must consent to use an effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR-T cells in vivo.

    Exclusion Criteria:
    1. Patients with isolated extramedullary relapse;

    2. Patients with confirmed diagnosis of Burkitt's lymphoma/ leukemia;

    3. Patients who had received prophylaxis for CNS leukemia within 1 week prior to Meta10-19 infusion;

    4. Patients with present or history of central nervous system diseases such as seizures disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;

    5. Patients with history of allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 6 months prior to Meta10-19 infusion;

    6. Patients who had received chemotherapy other than preconditioning chemotherapy within 2 weeks prior to Meta10-19 infusion ;

    7. Patients who participated in other clinical trials within 30 days prior to enrollment;

    8. Patients with active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, concomitant hepatitis B virus DNA level > 1000 copies/ml) or hepatitis C (HCV RNA positive);

    9. Patients with HIV antibody positive or treponema pallidum antibody positive;

    10. Patients with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g. positive blood cultures ≤72 hours before Meta10-19 infusion)

    11. Patients with unstable angina pectoris and/or myocardial infarction within 6 months prior to enrollment;

    12. Patients with history of other malignancies, but the following conditions can be enrollment:

    13. Adequately treated basal or squamous cell carcinoma (requiring adequate wound healing before signing informed consent);

    14. Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated therapeutically, has shown no signs of recurrence for at least 3 years prior to the signing of the informed consent;

    15. The primary malignancy has been completely resected and in complete remission for ≥5 years。

    16. Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age are positive);

    17. Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis);

    18. Other conditions that the investigator considered should not be enrolled in this clinical study, such as poor compliance.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Anhui Provincial Hospital Hefei Anhui China

    Sponsors and Collaborators

    • Anhui Provincial Hospital
    • Leman Biotech Co., Ltd

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Anhui Provincial Hospital
    ClinicalTrials.gov Identifier:
    NCT05747157
    Other Study ID Numbers:
    • Meta10-19-002
    First Posted:
    Feb 28, 2023
    Last Update Posted:
    Feb 28, 2023
    Last Verified:
    Feb 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Anhui Provincial Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 28, 2023