Clinical trial NCT05513612: Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies
Official title: Safety and Efficacy Study of Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
B-cell Non-Hodgkin's Lymphoma (B-NHL)
Multiple Myeloma (MM)
T-Cell Leukemia/Lymphoma, Adult
B-cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords: CD123 CAR-T
CD19 CAR-T
BCMA CAR-T
CD7 CAR-T
Hematopoietic and Lymphoid Malignancies
Lead sponsor: Shanghai Pudong Hospital
Sponsor class: OTHER
Collaborators: name: UTC Therapeutics Inc.
First posted: 2022-08-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the safety and efficacy of novel autologous CAR-T cells in patients with hematopoietic and lymphoid malignancies.

Detailed description: Chimeric antigen receptor (CAR)-modified T cells targeted CD19 have demonstrated unprecedented successes. Besides CD19, many other molecules such as CD123, BCMA, and CD7 may be potential in developing the corresponding CAR-T cells to treat patients with hematopoietic and lymphoid malignancies. UTC Therapeutics Inc. have developed an efficient platform for constructing CAR-T cells that can remodel of tumor microenvironment and enhance the anti-tumor immune response and persistence of CAR-T cells. In this study, all eligible subjects will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by investigational treatment, CAR-T cells. Safety, efficacy, pharmacokinetic, and pharmacodynamic of the CAR-T cells will be assessed.

Eligibility criteria: Inclusion Criteria:

1. Ability to understand and the willingness to sign informed consent.
2. Patients with relapsed or refractory Acute Myeloid Leukemia (AML), B-cell Non-Hodgkin's Lymphoma (B-NHL), Multiple Myeloma (MM), Adult T-cell Leukemia/Lymphoma (ATL), B-cell Acute Lymphoblastic Leukemia (B-ALL) after at least two cycles of first-line therapy or autologous hematopoietic stem cell transplantation (auto-HSCT).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0\~2.
4. Adequate organ functions:

   * Sufficient bone marrow function evaluated by investigator to receive lymphodepleting preparative regimen;
   * Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN), or creatinine clearance rate (as estimated by Cockcroft Gault) \> 30 mL/min/1.73 m\^2;
   * Alanine aminotransferase (ALT) ≤ 5×ULN; and total bilirubin (TBIL) \<2.0mg/dL; TBIL of patients with Gilbert's Syndrome or liver involvement must less than 3.0 mg/dL;
   * Left ventricular ejection fraction (LVEF) \> 40%.
5. Subjects who have previously received CD19 targeted therapy must have biopsy-proven lymphoma lesions still express CD19 antigen.

Exclusion Criteria:

1. Lymphomas involving only the central nervous system (CNS) (subjects with secondary CNS lymphomas are admitted).
2. History of another malignancy that has not been in remission for at least 2 year (the following conditions may be excluded from the 2-year restriction: non-melanoma skin cancer, completely resected stage I tumor with low probability of recurrence, limited-stage prostate cancer after treatment, biopsy-proven cervical carcinoma in situ, or PAP smear showing squamous epithelium internal lesions).
3. History of treatment with Alemtuzumab within 6 months prior to leukapheresis, or Fludarabine or Cladribine within 3 months prior to leukapheresis.
4. Active hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), or syphilis infection.
5. Uncontrolled fungal, bacterial, viral, or other infection.
6. Acute or chronic graft-versus-host disease (GVHD).
7. 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 stent, myocardial infarction, unstable angina, or other clinically significant heart disease.
8. History or clinical evidence of CNS disease.
9. Female subjects who are pregnant or lactating.
10. Prior CAR-T therapy or other genetically modified T cell therapy.

Primary outcomes:
measure: TEAEs
timeFrame: 4 weeks
measure: TRAEs
timeFrame: 4 weeks
measure: AESIs
timeFrame: 4 weeks
Secondary outcomes:
measure: Duration of Overall Response (DOR)
timeFrame: 12 months
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Overall survival (OS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center
state: Shanghai
Study officials:
affiliation: Shanghai Pudong Hospital
name: Zhiguo Long
role: PRINCIPAL_INVESTIGATOR
References: