Anti-CD19-CAR-T Cells in Subjects With Relapsed/Refractory B Cell Malignancies

NCT06532630 | Recruiting Early Phase 1

• 1 other identifier: CD19-CN-A5
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, open-label, exploratory study to determine the safety, tolerability, feasibility, and preliminary anti-tumor activity of anti-CD19-CAR-T cells in subjects with relapsed/refractory (r/r) B-cell malignancies. This study plans to enroll patients with relapsed/refractory CD19-positive B-cell malignancies, who will receive a single infusion of anti-CD19-CAR-T cells after screening, PBMC collection, and lymphodepleting chemotherapy.

Conditions

B-Cell Malignancy

Outcome Measures

Primary Outcomes (2)

• Safety and tolerance

  Incidence of dose-limiting toxicity (DLT)

  28 days after anti-CD19-CAR-T cells infusion

• Manufacturing feasibility

  Percentage of subjects for whom the required dose of anti-CD19-CAR-T cells can be successfully manufactured.

  1 year

Study Arms (1)

Anti-CD19-CAR-T cell therapy

EXPERIMENTAL

Investigational product: anti-CD19-CAR-T cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to anti-CD19-CAR-T cells infusion.

Genetic: Anti-CD19-CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Anti-CD19-CAR-T cells GENETIC

Each subject will be infused with single dose of anti-CD19-CAR-T cells. A classic "3+3" dose escalation will be employed.

Anti-CD19-CAR-T cell therapy

Fludarabine DRUG

Fludarabine will be given at a dose of 25 mg/m2/day intravenously (IV) for 3 days prior to anti-CD19-CAR-T cells infusion.

Anti-CD19-CAR-T cell therapy

Cyclophosphamide DRUG

Cyclophosphamide will be given at a dose of 250 mg/m2/day intravenously (IV) for 3 days prior to anti-CD19-CAR-T cells infusion.

Anti-CD19-CAR-T cell therapy

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent; ability and willingness to adhere to the study visit schedule and all protocol requirements.
• years old.
• Relapsed/refractory disease after standard treatment (including allogeneic/autologous hematopoietic stem cell transplantation) and not eligible for other treatment options such as a second hematopoietic stem cell transplant.
• A. Relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) is defined as one of the following:
• Primary refractory disease.
• Relapsed within 12 months after first remission.
• Relapsed or refractory after two or more lines of systemic therapy.
• Relapsed or refractory post allogeneic SCT. i. more than 100 days from the transplantation at the time of enrollment. ii. not receiving immunosuppressive drugs for 4 weeks prior to enrollment (≤5 mg prednisone or equivalent is allowed).
• B. Ph+ B-cell ALL are eligible if they are intolerant or ineligible for tyrosine kinase inhibitor (TKI) therapy or have relapse/refractory disease after at least two different TKI treatments.
• C. Relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) is defined as one of the following:
• No response to first-line therapy (primary refractory disease, excluding subjects intolerant to first-line therapy):
• PD is the best response after first-line therapy.
• Best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) is stable disease (SD), with rapid progression in 6 months.
• No response to second or subsequent lines of therapy:
• PD is the best response to last regimen.

You may not qualify if:

• If patients meet any of the following conditions, they cannot participate in this trial:
• Central nervous system (CNS) involvement in ALL and clinically significant neurological changes (CNS-2 and CNS-3):
• CNS-3, defined as detectable tumor cells in cerebrospinal fluid (CSF) with ≥ 5 white blood cells (WBCs) /mm3.
• CNS-2, defined as detectable tumor cells in CSF with \<5 WBCs /mm3. Note: Subjects with CNS-1 (no detectable tumor cells in CSF) or CNS-2 without evidence of clinically significant neurological changes are eligible for this study.
• CNS lymphoma confirmed by MRI; active CNS DLBL unless CNS involvement has been effectively treated (i.e., asymptomatic) and a local treatment interval of \> 4 weeks prior to enrollment.
• Active CNS diseases such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disorders, or any autoimmune diseases involving the central nervous system.
• Any malignancies other than CD19+ malignancies.
• Clinically significant heart disease or arrhythmias not controlled by medication.
• Ongoing or suspected fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotic therapy; simple urinary tract infections and simple bacterial pharyngitis are allowed.
• Hepatitis B (positive for hepatitis B surface antigen and hepatitis B DNA \>1000 copies/mL) and hepatitis C (positive for hepatitis C antibodies); syphilis, human immunodeficiency virus (HIV) infection.
• Presence of any indwelling or drainage catheter (e.g., percutaneous nephrostomy, indwelling Foley catheter, biliary drainage catheter, pleural/peritoneal/pericardial drainage catheter); the use of dedicated central venous access devices such as Port-A-Cath® or Hickman® catheters is allowed.
• Prior use of the following:
• CD19-targeted therapy.
• Chlorambucil or bendamustine within 3 months before enrollment, or PEG-asparaginase within 3 weeks before enrollment.
• live vaccines within 4 weeks before enrollment.

Sponsors & Collaborators

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

Study Sites (1)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

RECRUITING

MeSH Terms

Interventions

fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ge

  Thr First Affiliated Hospital of Anhui Medical University

  STUDY CHAIR

• Jian Ge, MD

  The First Affiliated Hospital of Anhui Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Long

CONTACT

055162923653; drlong1111@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 1, 2024
• Study Start: August 24, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 28, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)