Clinical Study of Chimeric CD(Cluster of Differentiation)138 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Multiple Myelomas
18 Years
80 Years
Both
Relapsed and/or Chemotherapy Resistant Multiple Myeloma
Trial Information
Clinical Study of Chimeric CD(Cluster of Differentiation)138 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Multiple Myelomas
PRIMARY OBJECTIVES:
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced
with the anti-CD138 vector (referred to as CART-138 cells).
II. Determine duration of in vivo survival of CART-138 cells. RT-PCR (reverse transcription
polymerase chain reaction) analysis of whole blood and bone marrow will be used to detect
and quantify survival of CART-138 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over
time.
SECONDARY OBJECTIVES:
I. For patients with detectable disease, measure anti-myeloma response due to CART-138 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-138 TCR zeta:CD137 and TCR zeta cells
over time.
III. Estimate relative trafficking of CART-138 cells in bone marrow.
IV. For patients with stored or accessible myeloma cells, determine myeloma cell killing by
CART-138 cells in vitro.
V. Determine if cellular or humoral host immunity develops against the murine anti-CD138,
and assess correlation with loss of detectable CART-138 (loss of engraftment).
VI. Determine the relative subsets of CART-138 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD138-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 CD138 positive multiple myeloma 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.
- CD138 positive multiple myeloma CR can not be achieved after at least 4 prior
combination chemotherapy regimens.
- MM 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. MM 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-008
NCT ID:
NCT01886976
Start Date:
June 2013
Completion Date:
June 2016
Related Keywords:
- Relapsed and/or Chemotherapy Resistant Multiple Myeloma
- multiple myeloma
- Multiple Myeloma
- Neoplasms, Plasma Cell
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