A Study of CAR T-Cells in Relapsed/Refractory Hematologic Malignancy

NCT06756321 | Recruiting Early Phase 1

• 1 other identifier: X01-CN-A1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label clinical trial of single-dose of CAR T-cells in subjects with relapsed/refractory hematologic malignancy.

Conditions

Relapsed/refractory Lymphoma; Relapsed/Refractory Leukemia

Outcome Measures

Primary Outcomes (2)

• Evaluate safety and tolerability of CAR T-cells

  Proportion of subjects experiencing dose-limiting toxicities (DLT)

  28 days after infusion of CAR T-cells

• Evaluate the feasibility of administration of CAR T-cells

  The proportion of subjects for whom the desired dose of CAR T-cells can be successfully manufactured

  12 months

Secondary Outcomes (9)

• Adverse events

  12 months

• Incidence of cytokine release syndrome (CRS) and neurotoxicity

  12 months

• Evaluate cellular kinetics and persistence of CAR T-cells

  28 days after CAR T infusion, after which the evaluation is at the discretion of investigator

• Preliminary anti-tumor effect

  12 months

• Overall response rate (ORR)

  12 months

Study Arms (1)

Cyclophosphamide + Fludarabine + CAR T-Cells

EXPERIMENTAL

Investigational product: anti-CD19-CAR T-cells, anti-CD30-CAR T-cell, anti-CD20/CD30-CAR T-cells. Subjects with CD19+ ALL or NHL will be infused with anti-CD19-CAR T-cells. Subjects with CD30+ HL or T-cell lymphoma will be infused with anti-CD30-CAR T-cells. Subjects with CD20+ lymphoma or CD20/CD30 double positive lymphoma who have relapsed after anti-CD19-CAR T-cell therapy will be infused with anti-CD20/CD30-CAR T-cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of CAR T-cells.

Biological: anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

anti-CD19-CAR T-cells, or anti-CD30-CAR T-cells, or anti-CD20/CD30-CAR T-cells BIOLOGICAL

Each subject will be infused with single dose. A classic "3+3" dose escalation will be employed. anti-CD19-CAR T-cells Dose level 1：1x10\^5 CAR T cells/kg, Dose level 2：3x10\^5 CAR T cells/kg, Dose level 3：1x10\^6 CAR T cells/kg anti-CD30-CAR T-cells Dose level 1：3x10\^6 CAR T cells/kg, Dose level 2：6x10\^6 CAR T cells/kg, Dose level 3：1x10\^7 CAR T cells/kg anti-CD20/CD30-CAR T-cells Dose level 1：1x10\^6 CAR T cells/kg, Dose level 2：3x10\^6 CAR T cells/kg, Dose level 3：1x10\^7 CAR T cells/kg

Cyclophosphamide + Fludarabine + CAR T-Cells

Fludarabine DRUG

Fludarabine will be given at a dose of 25 mg/m\^2/day intravenously (IV) for 3 days prior to the infusion of CAR T-cells.

Cyclophosphamide + Fludarabine + CAR T-Cells

Cyclophosphamide DRUG

Cyclophosphamide will be given at a dose of 250 mg/m\^2/day intravenously (IV) for 3 days prior to the infusion of CAR T-cells.

Cyclophosphamide + Fludarabine + CAR T-Cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for the study:
• Voluntarily participate in the clinical study. The individual or the legal guardian fully understands the study, sign the informed consent form (ICF), and is willing and able to follow and complete all trial procedures.
• Age ≥ 18 years and \< 70 years.
• Subjects with refractory or relapsed disease after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation) who are not suitable for other treatment options, such as a second stem cell transplant. The definitions of relapsed/refractory lymphoma include one of the following situations:
• a. Relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) is defined as one of the following:
• i) Primary refractory disease.
• ii) First relapse if the initial remission is ≤ 12 months.
• iii) Relapse or refractory disease after two or more lines of systemic therapy.
• iv) Relapse or refractory disease after allogeneic transplantation, provided that at the time of enrollment, the subject is at least 100 days post-stem cell transplantation and has not received immunosuppressive drugs for at least 4 weeks prior to enrollment, except for low-dose steroids (≤ 5 mg of prednisone or equivalent).
• b. Subjects with Ph+ B-cell ALL, who are intolerant to or ineligible for tyrosine kinase inhibitor (TKI) treatment, or who have relapsed/refractory disease after receiving at least two different TKI treatments, are eligible.
• c. Relapsed/refractory B-cell-derived non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) defined as one of the following:
• i) No response to first-line treatment (primary refractory disease, excluding subjects intolerant to first-line treatment);
• Disease progression (PD) as assessed after first-line treatment.
• Best response of SD after at least 4 cycles of first-line treatment (e.g., 4 cycles of RCHOP), with SD duration not exceeding 6 months after the last dose.
• ii) No response to second-line or more treatments.

You may not qualify if:

• Subjects are not eligible to participate in this study if they meet any of the following criteria:
• ALL patients with central nervous system (CNS) abnormalities, including CNS-2 and CNS-3 that are of clinically significant neurological changes:
• CNS-3 disease is defined as detectable tumor cells in the cerebrospinal fluid (CSF) sample with ≥ 5 WBCs/mm\^3, with or without neurological changes.
• CNS-2 disease is defined as detectable tumor cells in the CSF sample with \< 5 WBCs/mm\^3 and with neurological changes.
• Note: Subjects classified as CNS-1 (no detectable tumor cells in CSF) and those with no clinically significant neurological changes classified as CNS-2 are eligible to participate in this study.
• Brain MRI evidence shows central nervous system lymphoma. Active primary central nervous system DLBL, unless CNS involvement has been effectively treated (i.e., participants are asymptomatic) and there has been a local treatment interval of \>4 weeks prior to enrollment.
• Presence of active central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with CNS involvement.
• A history of or concurrent presence of other malignancies.
• Clinically significant cardiac disease or arrhythmias that cannot be controlled with medication.
• Presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotics for treatment. Uncomplicated urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
• Positive for hepatitis B (positive for HBsAg, and/or positive for Hepatitis B core antibody and HBV DNA \>1000 copies/mL) and hepatitis C (positive for HCV antibodies), syphilis or human immunodeficiency virus (HIV) infection.
• Presence of any indwelling or drainage catheters (such as percutaneous nephrostomy tubes, indwelling Foley catheters, bile drainage tubes, or pleural/peritoneal/pericardial catheters). The use of specialized central venous access devices, such as Port-A-Cath® or Hickman® catheters, is allowed.
• Prior medication:
• Use of clofarabine or cladribine within 3 months prior to enrollment, or use of PEG-asparaginase within 3 weeks prior to enrollment.
• Injection of live vaccines within 4 weeks prior to enrollment.

Sponsors & Collaborators

• Affiliated Hospital of Nantong University: lead
• Shanghai First Song Biotechnology Co., LTD: collaborator

Study Sites (1)

Affiliated Hospital of Nantong University

Nantong, Jiangsu, 226001, China

RECRUITING

Related Publications (1)

• Huang Y, Gong Y, Liu X, Ruan H, Lu J, Kouros-Mehr H, Liu H, Wang H. Case Report: Bispecific CD20/CD30-targeted chimeric antigen receptor T-cell therapy for non-Hodgkin's lymphoma. Front Immunol. 2025 May 8;16:1567149. doi: 10.3389/fimmu.2025.1567149. eCollection 2025.

  PMID: 40406106 DERIVED

MeSH Terms

Conditions

Lymphoma; Leukemia

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Hong Liu, MD

  Affiliated Hospital of Nantong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hong Liu, MD

CONTACT

+86-13951300660; hongliu63@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of the Division of Hematology

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: January 3, 2025
• Study Start: September 18, 2023
• Primary Completion: March 18, 2025
• Study Completion: March 18, 2026
• Last Updated: January 3, 2025

Record last verified: 2024-12

Locations

CN (1)