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

• Sponsor: Duke University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00814983
• Collaborator: (none)
• Enrollment: 15
• Arms: 2
• Duration (Months): 74.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
ALL; ANLL; MDS; NHL	Procedure: Naive T-cell Depleted Stem Cell Transplant; Procedure: Stem Cell Transplant No Manipulation; Device: Isolex device from Baxter	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Myeloablative Allogeneic Stem Cell Transplantation Using a Naive T-Cell Depleted Peripheral Blood Stem Cell Graft
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. The Incidence of Grade II-IV Acute Graft Versus Host Disease [One year from date of transplant]

2. Disease Free Survival [One year]

Secondary Outcome Measures

1. Rate of Immune Recovery [3 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

No locations specified.

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Mitchell Horwitz, MD, Duke Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00814983
• Other Study ID Numbers: Pro00000993
• First Posted: Dec 29, 2008
• Last Update Posted: Nov 25, 2013
• Last Verified: Sep 1, 2013

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

Study Results

Participant Flow

Arm/Group Title	Stem Cell Transplant No Manipulation	Naive T-cell Depleted Stem Cell Transplant
Arm/Group Description	Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation	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.
Period Title: Overall Study
STARTED	15	0
COMPLETED	12	0
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Stem Cell Transplant No Manipulation	Naive T-cell Depleted Stem Cell Transplant	Total
Arm/Group Description	Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation	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.	Total of all reporting groups
Overall Participants	15	0	15
Age (participants) [Number]
<=18 years	0 0%	0 NaN
Between 18 and 65 years	15 100%	15 Infinity
>=65 years	0 0%	0 NaN
Gender (participants) [Number]
Female	8 53.3%	8 Infinity
Male	7 46.7%	7 Infinity
Region of Enrollment (participants) [Number]
United States	15 100%	15 Infinity

Outcome Measures

1. Primary Outcome

Title	The Incidence of Grade II-IV Acute Graft Versus Host Disease
Time Frame	One year from date of transplant

Outcome Measure Data

Analysis Population Description

No analysis was performed since the experimental arm was not opened

Arm/Group Title	Stem Cell Transplant No Manipulation	Naive T-cell Depleted Stem Cell Transplant
Arm/Group Description	Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation	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.
Measure Participants	0	0

2. Primary Outcome

Title	Disease Free Survival
Time Frame	One year

Outcome Measure Data

Analysis Population Description

No analysis was performed since the experimental arm was not opened

Arm/Group Title	Stem Cell Transplant No Manipulation	Naive T-cell Depleted Stem Cell Transplant
Arm/Group Description	Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Rate of Immune Recovery
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

No analysis was performed since the experimental arm was not opened

Arm/Group Title	Stem Cell Transplant No Manipulation	Naive T-cell Depleted Stem Cell Transplant
Arm/Group Description	Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation	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.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse event analysis was not undertaken due to stopping the study prior to enrolling in the experimental arm.
Arm/Group Title	Stem Cell Transplant No Manipulation		Naive T-cell Depleted Stem Cell Transplant
Arm/Group Description	Control: Cohort 1 Stem Cell Transplant No Manipulation will receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation		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.
All Cause Mortality
	Stem Cell Transplant No Manipulation		Naive T-cell Depleted Stem Cell Transplant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stem Cell Transplant No Manipulation		Naive T-cell Depleted Stem Cell Transplant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Stem Cell Transplant No Manipulation		Naive T-cell Depleted Stem Cell Transplant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.