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Treatment of Relapsed and/or Chemotherapy Refractory CD33 Positive Acute Myeloid Leukemia by CART-33 (CART33)

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ClinicalTrials.gov Identifier: NCT01864902
Recruitment Status : Unknown
Verified January 2016 by Han weidong, Chinese PLA General Hospital.
Recruitment status was:  Recruiting
First Posted : May 30, 2013
Last Update Posted : January 28, 2016
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital

Brief Summary:

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.


Condition or disease Intervention/treatment Phase
Relapsed Adult Myeloid Leukemia Chemotherapy Refractory Adult Myeloid Leukemia Biological: CART33 cells Biological: anti-CD33 CART Biological: anti-CD33 CAR T cells Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD33 vector (referred to as CART-33 cells).

II. Determine duration of in vivo survival of CART-33 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-33 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-leukemia response due to CART-33 cell infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-33 TCR zeta:CD137 and TCR zeta cells over time.

III. Estimate relative trafficking of CART-33 cells in bone marrow.

IV. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by CART-33 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD33, and assess correlation with loss of detectable CART-33 (loss of engraftment).

VI. Determine the relative subsets of CART-33 T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 group according to order of enrollment.

Patients receive anti-CD33-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
Study Start Date : April 2013
Estimated Primary Completion Date : April 2016
Estimated Study Completion Date : April 2017


Arm Intervention/treatment
Experimental: anti-CD33 CAR T cells
Patients receive anti-CD33-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
Biological: CART33 cells
genetically modified lymphocyte therapy
Other Name: chimeric antigen receptor T cells with specificity for CD33

Biological: anti-CD33 CART
Other Name: CART33

Biological: anti-CD33 CAR T cells



Primary Outcome Measures :
  1. Occurrence of study related adverse events [ Time Frame: Until week 24 ]
    defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment


Secondary Outcome Measures :
  1. Anti-leukemia responses to CART-33 cell infusions [ Time Frame: up to 24 weeks ]

Other Outcome Measures:
  1. in vivo existence of CART33 [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled

    • CD33+ acute myeloid leukemia CR can not be achieved after at least 2 prior combination chemotherapy regimens.

AML in CR(complete remission)2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.

Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).

Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.

Residual disease after primary therapy and not eligible for autologous SCT

  • Expected survival > 12 weeks
  • Creatinine < 2.5 mg/dl
  • ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
  • Bilirubin < 2.0 mg/dl
  • Any relapse after prior SCT will make patient eligible regardless of other prior therapy
  • Adequate venous access for apheresis, and no other contraindications for leukapheresis
  • Voluntary informed consent is given

Exclusion Criteria:

  • Pregnant or lactating women

    • The safety of this therapy on unborn children is not known
    • Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
    • Uncontrolled active infection
    • Active hepatitis B or hepatitis C infection
    • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
    • Previously treatment with any gene therapy products
    • Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation
    • Any uncontrolled active medical disorder that would preclude participation as outlined
    • HIV infection

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): NCT01864902


Contacts
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Contact: Weidong Han, Dr. 86-10-13651392893 hanwdrsw@sina.com
Contact: Xuliang Shen, Dr. 86-355-13015365546 shenxlcyp@sohu.com

Locations
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China, Beijing
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital, Hematological Department, Affiliated Hospital of Changzhi Medical College Recruiting
Beijing, Beijing, China, 100853
Contact: Weidong Han, Dr.    86-10-13651392893    hanwdrsw@sina.com   
Contact: Xuliang Shen, Dr.    86-355-13015365546    shenxlcyp@sohu.com   
Sub-Investigator: Ying Liu, Dr.         
Sub-Investigator: Yao Wang, Dr.         
Sponsors and Collaborators
Chinese PLA General Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Han weidong, PI, Chinese PLA General Hospital
ClinicalTrials.gov Identifier: NCT01864902     History of Changes
Other Study ID Numbers: CHN-PLAGH-BT-006
First Posted: May 30, 2013    Key Record Dates
Last Update Posted: January 28, 2016
Last Verified: January 2016
Keywords provided by Han weidong, Chinese PLA General Hospital:
CD33 positive acute myeloid leukemia (AML)
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms