Study of CAR-T Cell Therapy in the Treatment of Relapsed/Refractory Hematological Malignancies

The Affiliated People's Hospital of Ningbo University

Status and phase: Enrolling; Phase 1

Conditions: Lymphoma; Myeloma; Leukemia; Relapsed/Refractory Hematological Malignancies

Treatments: Drug: Cyclophosphamide; Biological: Autologous CAR-T cells; Drug: Fludarabine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05528887

2021-037

Details and patient eligibility

About

The primary purpose of this study is to determine the safety and efficacy of novel autologous CAR-T cells in patients with relapsed/refractory hematological malignancies.

Full description

CAR-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 and efficacy of the CAR-T cells will be assessed.

Enrollment: 10 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histological diagnosis of hematological malignancies (such as lymphoma, myeloma, leukemia) refractory to, or relapsing after standard therapy.

2. Positive expression of specific antigens.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0~2.

4. Adequate organ functions:

   • Serum bilirubin ≤ 35 μmol/L;
   • Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2;
   • Serum creatinine (Cr) ≤ 2 × upper limit of normal (ULN);
   • Brain natriuretic peptide (BNP)<80 pg/mL.

5. Subjects must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.

Exclusion criteria

1. History of allergy to any of the drugs involved in the protocol.

2. History of cardiac diseases:

   • Left ventricular ejection fraction (LVEF) < 50%;
   • Class III or IV heart failure as defined by the New York Heart Association (NYHA).

3. History of another malignancy tumor.

4. Active hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), or syphilis infection.

5. Patients with any contraindications to allogeneic hematopoietic stem cell transplantation.

6. Uncontrolled fungal, bacterial, viral, or other infection.

7. Female subjects who are pregnant or lactating.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

10 participants in 1 patient group

Autologous CAR-T cells

Experimental group

Description:

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR-T cells. CAR-T cells targeted CD19/BCMA/CD123/CD7 are autologous genetically modified T cells.

Treatment:

Drug: Fludarabine

Biological: Autologous CAR-T cells

Drug: Cyclophosphamide