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Myeloablative Allogeneic Stem Cell Transplantation Using a Naive T-Cell Depleted Peripheral Blood Stem Cell Graft

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00814983
First received: December 26, 2008
Last updated: February 20, 2013
Last verified: February 2013
History of Changes
  Purpose

The primary objectives will be to measure the safety and efficacy of allogeneic stem cell transplantation using a peripheral blood stem cell graft that has been depleted of CD45RA+ Naive T-cells.

The secondary objectives will be to measure the pace of immune recovery.


Condition Intervention Phase
ALL
ANLL
MDS
NHL
 Procedure: Naive T-cell Depleted Stem Cell Transplantation
Other: Control Arm: Stem Cell Transplant No Manipulation
Device: Isolex device from Baxter
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Myeloablative Allogeneic Stem Cell Transplantation Using a Naive T-Cell Depleted Peripheral Blood Stem Cell Graft

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:
  • The incidence of grade II/IV acute graft versus host disease and one year disease-free survival. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The kinetics and proliferation response to mitogens of T cells; B cell and NK cell recovery will be monitored, as will the incidence of opportunistic infections, chronic Graft Versus Host Disease and 100-day Treatment-Related Mortality. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 57
Study Start Date: July 2007
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 2
29 subjects will be enrolled on this arm and compared to the historical control
 Procedure: Naive T-cell Depleted Stem Cell Transplantation
The Isolex device from Baxter will be used to perform the cell selection procedure. After the CD34 selected stem cell graft has been collected, the CD34- "flow-through"fraction will be depleted of CD45RA+ naive T-cells. To accomplish this, a second immunomagnetic bead selection process will be performed on the Isolex device, making use of a GMP-grade murine anti-human CE45RA antibody. This depleted fraction will comprise the donor lymphocyte inoculum given to the transplant recipient along with the stem cell component on day 0 of transplant.
Device: Isolex device from Baxter
Active Comparator: Cohort 1 Historical Control
12 subjects as a historical control
 Other: Control Arm: Stem Cell Transplant No Manipulation
These patients will be transplanted with unmanipulated peripheral blood stem cells.

Detailed Description:

A cohort of patients (Cohort 1) will be enrolled to receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation. With the exception of volume and/or plasma depletion (in cases of donor/recipient ABO incompatibility), the peripheral blood stem cell graft will be unmodified. The primary purpose of Cohort 1 is to prospectively collect samples for measurement of immune recovery from a relatively homogeneous population of patients treated in a uniform manner. Within the limitations of age-matching, patients accrued to Cohort 1 will be incorporated into a larger retrospective historical control group for purposes of comparison with Cohort 2 of the incidence of grade II-IV acute Graft versus Host disease. The experimental aspects of this trial will be the use of a naïve T-cell depleted peripheral blood stem cell graft (Cohort 2). All other aspects of this stem cell transplantation are in line with the standard of care. Recruitment to this trial will be stratified by donor type as matched sibling or matched unrelated donor. Patients will be conditioned with total body irradiation (1350cGy) and Cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 6/6 HLA-identical family members or 8/8 (HLA A, B, C, DRB1) allele-level matched unrelated donors.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 to 65 years.
  • 8/8 or 7/8 HLA-identical matched sibling OR Allele level 8/8 (HLA-A, B, C, DRbeta1) matched unrelated donor.
  • Patients with high risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22) or t(1;19) or patients presenting with extreme hyperleukocytosis (WBC>500,000/ml) or partial remission after initial induction therapy.
  • Adult patients with acute non-lymphocytic Leukemia (ANLL) in first complete remission with high-risk cytogenetics (monosomy chromosome 5 or 7, del(5q), abn(3q26), complex karyotypic abnormalities) or failure to achieve complete remission after standard induction therapy.
  • All patients with ALL or ANLL in second or subsequent remission or partial remission (<5% blasts in bone marrow as measured by flow cytometry).
  • All patients with CML in chronic (failed interferon and/or Gleevec) or accelerated phase.
  • Patients with myelodysplastic syndrome with International Prognostic Scoring System (IPSS) risk category of INT-1 or greater.
  • Myelofibrosis with myeloid metaplasia
  • Patients with severe aplastic anemia must have failed immunosuppressive therapy such as cyclosporine plus anti-thymocyte globulin.
  • Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.
  • ECOG performance status <2
  • Patients must have adequate function of other organ systems as measured by:
  • Creatinine clearance (by Cockcroft Gault equation [Appendix IV]) > 30ml/min. Hepatic transaminases (ALT/AST) < 4 x normal, bilirubin < 2.0 mg/dl.
  • Pulmonary function tests demonstrating FVC and FEV1 of >50% of predicted for age and DLCO > 50% of predicted.
  • Ejection fraction of >45% by echocardiogram, radionuclide scan or cardiac MRI.
  • Patients must be HIV negative.
  • Patients must not be pregnant.

Exclusion Criteria:

  • Patients with > 5% blasts in bone marrow or peripheral circulation.
  • Patients with rapidly progressive ANLL or ALL.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00814983

Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Mitchell Horwitz, MD Duke University Health System
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00814983     History of Changes
Other Study ID Numbers: Pro00000993
Study First Received: December 26, 2008
Last Updated: February 20, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
myeloablative
stem cell
naive T-cell depleted
allogeneic

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on May 23, 2013