Clinical trial NCT05239689: Clinical Study of CD38 CAR-T Cells in the Treatment of Hematological Malignancies
Official title: Clinical Study on the Safety and Effectiveness of CD38 CAR-T Cells in the Treatment of CD38-positive Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: AML
Keywords: AML
CD38 CAR T-cell therapy
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2022-02-15
Enrollment: 36
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Clinical Study on the Safety and Effectiveness of CD38 CAR-T Cells in the Treatment of CD38-positive Hematological Malignancies

Detailed description: The CAR-T cell injection uses immune cells from healthy donors, and is the final product obtained after CAR genetic modification, cell expansion, culture, screening, preparation, sub-packaging, and release inspection. CD38 is highly expressed in myeloid leukemia, and it has been confirmed that the treatment of targeting CD38 has great potential in the treatment of CD38-positive hematological malignancies. The center intends to apply for a clinical trial of CD38 CAR-T cells to treat CD38-positive hematological malignancies on the basis of preliminary research.

Eligibility criteria: Inclusion Criteria:

* 1. Patients is histologically diagnosed with CD38-positive AML according to the NCCN Clinical Practice Guidelines in Oncology：Acute Myeloid Leukemia（Version 2.2021）;
* 2. The diagnosis is consistent with r/r CD38 + AML, and includes any of the following conditions:

  1. No CR was obtained after 2 courses of standard chemotherapy
  2. The first induction was CR, but the duration of CR was less than 12 months
  3. No CR was obtained after the first or multiple remedial treatment
  4. Relapse twice or more
* 3. The number of blast cells in bone marrow was more than 5% (morphology) and / or \> 1% (flow cytometry);
* 4. No active lung infection, inhaled air oxygen saturation ≥92%;
* 5. The estimated survival time is more than 3 months;
* 6. ECOG score was 0-2;
* 7. The patients or their legal guardians voluntarily participated in the trial and signed the informed consent.

Exclusion Criteria:

* 1. Patients with history of epilepsy or other central nervous system diseases;
* 2. Patients with prolonged QT or severe heart disease;
* 3. Pregnant or lactating women (the safety of this therapy for unborn children is unknown);
* 4. The patients with uncontrolled active infection;
* 5. Active hepatitis B or hepatitis C virus infection;
* 6. Previous application of gene therapy;
* 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
* 8. Serum creatinine \> 2.5mg/dl or ALT / AST \> 3 times ULN or bilirubin \> 2.0mg/dl;
* 9. Those who suffer from other uncontrolled diseases are not suitable to join the study;
* 10. HIV infection;
* 11. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CD38 CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 90 days after CD38 CAR T-cells infusion
Secondary outcomes:
measure: Concentration of CAR-T cells
timeFrame: From admission to the end of the follow-up, up to 2 years
measure: Disease control rate, DCR
timeFrame: From Day 28 CD38 CAR-T infusion up to 2 years
measure: Duration of remission, DOR
timeFrame: 24 months post CD38 CAR-T cells infusion
measure: Progression-free survival, PFS
timeFrame: 24 months post CD38 CAR-Tcells infusion
measure: Overall survival, OS
timeFrame: From CD38 CAR-T infusion to death，up to 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, PhD
role: PRINCIPAL_INVESTIGATOR
References: