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

February 27, 2023 updated by: Shanghai Pudong Hospital

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201399
        • Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Cyclophosphamide
Administered according to package insert
Other Names:
  • Cytoxan
Drug: Fludarabine
Administered according to package insert
Other Names:
  • Fludara
Biological: Autologous CAR-T cells
CAR-T cells will be infused intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TEAEs
Time Frame: 4 weeks
Incidence and severity of Treatment Emergent Adverse Event.
4 weeks
TRAEs
Time Frame: 4 weeks
Incidence and severity of Treatment Related Adverse Events.
4 weeks
AESIs
Time Frame: 4 weeks
Incidence and severity of AEs of Special Interest.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Overall Response (DOR)
Time Frame: 12 months
Time from documentation of disease response to disease progression.
12 months
Progression-Free Survival (PFS)
Time Frame: 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.
12 months
Overall survival (OS)
Time Frame: 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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Pudong Hospital

Collaborators

UTC Therapeutics Inc.

Investigators

  • Principal Investigator: Zhiguo Long, Shanghai Pudong Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Anticipated)

December 31, 2025

Study Completion (Anticipated)

December 31, 2026

Study Registration Dates

First Submitted

August 22, 2022

First Submitted That Met QC Criteria

August 22, 2022

First Posted (Actual)

August 24, 2022

Study Record Updates

Last Update Posted (Actual)

March 1, 2023

Last Update Submitted That Met QC Criteria

February 27, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-IIT-002-E03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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