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

Phase 1

Recruiting

• Conditions: Relapsed/Refractory Hematological Malignancies; Lymphoma; Myeloma; Leukemia
• Interventions: Biological: Autologous CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT05528887
• Lead Sponsor: The Affiliated People's Hospital of Ningbo University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2021-09-16
• Status Verified: 2022-09
• Study First Submitted: 2022-09-01
• Study First Submitted QC: 2022-09-01
• Last Update Submitted: 2022-09-01
• Study First Posted: 2022-09-06
• Last Update Posted: 2022-09-06
• Primary Completion: 2024-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous CAR-T cells	Autologous CAR-T cells	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.
Autologous CAR-T cells	Fludarabine	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.
Autologous CAR-T cells	Cyclophosphamide	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.

Primary Outcome Measures

Name	Time	Method
TEAEs	4 weeks	Incidence and severity of Treatment Emergent Adverse Event.
TRAEs	4 weeks	Incidence and severity of Treatment Related Adverse Events.
AESIs	4 weeks	Incidence and severity of AEs of Special Interest.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) (PR+CR)	12 months	The proportion of patients with complete response(CR) or partial response(PR)
Progression-Free Survival (PFS)	12 months	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.
Overall survival (OS)	12 months	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.

Trial Locations

Locations (1)

The Affiliated People's Hospital of Ningbo University; 🇨🇳 Ningbo, Zhejiang, China