Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT

June 13, 2017 updated by: Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences

Donor-derived Anti-CD123 Chimeric Antigen Receptors Modified T Cells for Recurred Acute Myeloid Leukaemia After Allogeneic Hematopoietic Stem Cell Transplantation

Patients with acute myeloid leukemia(AML) recurred after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis.The investigators developed donor-derived chimeric antigen receptor modified-T cell(CART) to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to treat recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Allo-HSCT is increasingly being used for AML, however, leukemia relapse remain a main problem for decades.Recently the investigators have witnessed great progresses in cancer therapy with chimeric antigen receptors modified T cells(CAR-T), especially for B-cell malignance. preclinical data about anti-CD123 CART have shown raised serious safety concerns of human anti-CD123 CAR-T for severe impairment of normal hematopoiesis in NSG mice.Patients with AML recurred after allo-HSCT have a dismal prognosis.The investigators developed donor-derived CART to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.

Study Type

Interventional

Enrollment (Anticipated)

20

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 Contact Backup

  • Name: Bin Zhang, M.D., Ph.D.
  • Phone Number: +86-010-6694-7125
  • Email: zb307ctc@163.com

Study Locations

  • China
      • Beijing Shi, China
        • Recruiting
        • Fengtai District
        • Contact:

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male and Female subjects with CD123+ acute myeloid leukemia as confirmed by immunohistochemistry and flow cytometry;
  2. Patients must have received an allogenic stem cell transplantation(Allo-HSCT). The leukemia relapsed. There are available donor or enough cryopreserved donor-derived PBMCs for CART preparation and subsequent Allo-HSCT. In the previous case, the donor should have adequate venous access for apheresis.
  3. Karnofsky score greater than 70%;
  4. patients more than 18 years of age
  5. Expected survival time >16 weeks;
  6. Bilirubin <3.0 mg/dL,
  7. Alanine aminotransferase(ALT)/ aspartate aminotransferase(AST)<3 fold normal.
  8. Diffusing capacity of the lung for carbon monoxide(DLCO) and forced expiratory volume in one second(FEV1)>45% of predictive value.
  9. At least received three kinds of medicines functioning by different mechanisms, including alkylating agents, protease inhibitors, and immunomodulators, and disease progressing within 60 days.
  10. Important organs are well tolerated;
  11. For post-transplantation patients, the apheresis would be undertaken only at least 2 weeks after immunosuppressive agents for GvHD withdrawal;
  12. From very beginning of the test to 30 days after the withdrawal, men and women should adopt reliable contraceptive measures.
  13. All research participants must have the ability to understand and willingness to sign a written informed consent.

Exclusion criteria:

  1. Patients were diagnosed with APL M3:t(15; 17)(q22; q12);PML/RARα ）；
  2. Symptomatic active central nervous system leukaemia;
  3. Patients with HIV, hepatitis B or C infection;
  4. Any concurrent active malignancies;
  5. Other uncontrolled active illness that hinders participation in the trial;
  6. Patients suffer from coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious heart, cerebrovascular disease;
  7. patients with poorly controlled hypertensive
  8. patients with froward psychiatric history
  9. anyone who the researchers think unsuitable to participate in the investigation;
  10. anyone who long-term use of immunosuppressive agents for organ transplants or other reasons, or undertake inhaled corticosteroids therapy recently.
  11. failed production release testing: CAR+ T cells <30% or T cell expansion less than 5-fold under the CD3/28 beads stimulation.
  12. Pregnant, lactating or female patients planning to get pregnant within 2 months before treatment ends;

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: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells
Patients will receive a full dose CART infusion at day 0.
Biological: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells
a single dose of CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells will be infusion after preconditioning.
Other Names:
  • anti-CD123 CART, CART123

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03
Time Frame: 15 years
15 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 15 years
15 years
CART cells persistence in vivo
Time Frame: 15 years
15 years
CAR123-specific antibody level
Time Frame: 15 years
15 years
Disease response(CR, CRi)
Time Frame: 15 years
15 years

Collaborators and Investigators

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

Sponsor

Affiliated Hospital to Academy of Military Medical Sciences

Investigators

  • Study Director: Hu Chen, M.D., Ph.D., Affiliated Hospital to Academy of Military Medical Sciences, China

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)

March 25, 2017

Primary Completion (Anticipated)

March 18, 2019

Study Completion (Anticipated)

March 18, 2021

Study Registration Dates

First Submitted

March 21, 2017

First Submitted That Met QC Criteria

April 10, 2017

First Posted (Actual)

April 14, 2017

Study Record Updates

Last Update Posted (Actual)

June 14, 2017

Last Update Submitted That Met QC Criteria

June 13, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 307-RV-CAR-123

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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