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

NCT00814983 | Terminated Phase 1 Results DMC

• 1 other identifier: Pro00000993
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

ALL; ANLL; MDS; NHL

Keywords

myeloablative; stem cell; naive T-cell depleted; allogeneic

Outcome Measures

Primary Outcomes (2)

• The Incidence of Grade II-IV Acute Graft Versus Host Disease

  One year from date of transplant

• Disease Free Survival

  One year

Secondary Outcomes (1)

• Rate of Immune Recovery

  3 years

Study Arms (2)

Naive T-cell Depleted Stem Cell Transplant

EXPERIMENTAL

Experimental: Cohort 2 will receive a T-cell depleted peripheral blood stem cell graft. All other aspects of this stem cell transplantation are in line with the standard of care.

Procedure: Naive T-cell Depleted Stem Cell Transplant; Device: Isolex device from Baxter

Stem Cell Transplant No Manipulation

ACTIVE COMPARATOR

Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation

Procedure: Stem Cell Transplant No Manipulation

Interventions

Naive T-cell Depleted Stem Cell Transplant PROCEDURE

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.

Naive T-cell Depleted Stem Cell Transplant

Stem Cell Transplant No Manipulation PROCEDURE

These patients will be transplanted with unmanipulated peripheral blood stem cells.

Stem Cell Transplant No Manipulation

Isolex device from Baxter DEVICE

Naive T-cell Depleted Stem Cell Transplant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years.
• /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.

You may not qualify if:

• Patients with \> 5% blasts in bone marrow or peripheral circulation.
• Patients with rapidly progressive ANLL or ALL.

Sponsors & Collaborators

• Duke University: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Mitchell Horwitz, MD
• Organization: Duke University Medical Center

Mitchell.Horwitz@duke.edu

919-668-1045

Study Officials

• Mitchell Horwitz, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2008
• First Posted: December 29, 2008
• Study Start: July 1, 2007
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: November 25, 2013
• Results First Posted: November 25, 2013

Record last verified: 2013-09