Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

Safety and Efficacy Study of Novel CAR-T Cell Therapy in the Treatment of Hematopoietic and Lymphoid Malignancies

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05513612
• Other study ID #: 2020-IIT-002-E03
• Status: Withdrawn
• Phase: Phase 1
• Start date: August 1, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2023
• Source: Shanghai Pudong Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• B-cell Acute Lymphoblastic Leukemia (B-ALL)
• Leukemia
• Leukemia, Myeloid, Acute
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, B-Cell
• Multiple Myeloma
• Multiple Myeloma (MM)
• Neoplasms
• Neoplasms, Plasma Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Autologous CAR-T cells
CAR-T cells will be infused intravenously.

Drug:
• Fludarabine
Administered according to package insert
• Cyclophosphamide
Administered according to package insert

Locations

Country	Name	City	State
China	Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Pudong Hospital	UTC Therapeutics Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TEAEs	Incidence and severity of Treatment Emergent Adverse Event.	4 weeks
Primary	TRAEs	Incidence and severity of Treatment Related Adverse Events.	4 weeks
Primary	AESIs	Incidence and severity of AEs of Special Interest.	4 weeks
Secondary	Duration of Overall Response (DOR)	Time from documentation of disease response to disease progression.	12 months
Secondary	Progression-Free Survival (PFS)	PFS was defined as the time from CAR-T infusion to the date of disease progression or death from any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.	12 months
Secondary	Overall survival (OS)	OS was defined as the time from CAR-T infusion to the date of death. Participants who did not die by the analysis data cutoff date were censored at their last contact date.	12 months