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

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ClinicalTrials.gov Identifier: NCT03114670
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Adult Acute Myeloid Leukemia Biological: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Donor-derived Anti-CD123 Chimeric Antigen Receptors Modified T Cells for Recurred Acute Myeloid Leukaemia After Allogeneic Hematopoietic Stem Cell Transplantation
Actual Study Start Date : March 25, 2017
Estimated Primary Completion Date : March 18, 2019
Estimated Study Completion Date : March 18, 2021


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 Name: anti-CD123 CART, CART123




Primary Outcome Measures :
  1. Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03 [ Time Frame: 15 years ]

Secondary Outcome Measures :
  1. CART cells persistence in vivo [ Time Frame: 15 years ]
  2. CAR123-specific antibody level [ Time Frame: 15 years ]
  3. Overall survival [ Time Frame: 15 years ]
  4. Disease response(CR, CRi) [ Time Frame: 15 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03114670


Contacts
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Contact: Hu Chen, M.D., Ph.D. +86-010-6694-7108 chenhu217@aliyun.cn
Contact: Bin Zhang, M.D., Ph.D. +86-010-6694-7125 zb307ctc@163.com

Locations
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China
Fengtai District Recruiting
Beijing Shi, China
Contact: Hu Chen, M.D., Ph.D.    +86-010-6694-7108    chenhu217@aliyun.com   
Sponsors and Collaborators
Affiliated Hospital to Academy of Military Medical Sciences
Investigators
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Study Director: Hu Chen, M.D., Ph.D. Affiliated Hospital to Academy of Military Medical Sciences, China
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Responsible Party: Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences
ClinicalTrials.gov Identifier: NCT03114670    
Other Study ID Numbers: 307-RV-CAR-123
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: June 14, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences:
Leukemia
Leukemia, Myeloid
Recurrence
Neoplasms by Histologic Type
Disease Attributes
Cyclophosphamide
Fludarabine
CD123
Chimeric Antigen Receptor modified T-cells
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms