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

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.

Study Overview

• Status: Terminated
• Conditions: MDS; NHL; ALL; ANLL
• Intervention / Treatment: Procedure: Naive T-cell Depleted Stem Cell Transplant; Device: Isolex device from Baxter; Procedure: Stem Cell Transplant No Manipulation

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Naive T-cell Depleted Stem Cell Transplant; 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; 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: Stem Cell Transplant No Manipulation; 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; These patients will be transplanted with unmanipulated peripheral blood stem cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Incidence of Grade II-IV Acute Graft Versus Host Disease	One year from date of transplant
Disease Free Survival	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Immune Recovery	The time to recovery of T-cell subset, B cell and NK cell recovery will be monitored along with T-Cell proliferative response to mitogens.	3 years

Collaborators and Investigators

• Sponsor: Duke University

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: December 26, 2008
• First Submitted That Met QC Criteria: December 26, 2008
• First Posted (ESTIMATE): December 29, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2013
• Last Update Submitted That Met QC Criteria: September 25, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: stem cell; allogeneic; myeloablative; naive T-cell depleted
• Other Study ID Numbers: Pro00000993