Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
5 Years
90 Years
Both
Relapsed Adult Myeloid Leukemia, Chemotherapy Refractory Adult Myeloid Leukemia
Trial Information
Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Occurrence of study related adverse events
Outcome Description:
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Outcome Time Frame:
Until week 24
Safety Issue:
Yes
Authority:
China: Ethics Committee
Study ID:
CHN-PLAGH-BT-006
NCT ID:
NCT01864902
Start Date:
April 2013
Completion Date:
April 2017
Related Keywords:
- Relapsed Adult Myeloid Leukemia
- Chemotherapy Refractory Adult Myeloid Leukemia
- CD33 positive acute myeloid leukemia (AML)
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
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