CD34+Selection for Partially Matched Family or Matched Unrelated Adult Donor Transplant

Sponsor

New York Medical College (Other)

Overall Status

Completed

CT.gov ID

NCT01049854

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CD34+ stem cell selection in children, adolescents and young adults receiving partially matched family donor or matched unrelated adult donor allogeneic bone marrow or peripheral blood stem cell transplant will be safe and well tolerated and be associated with a low incidence of serious (Grade III/IV) acute and chronic graft versus host disease (GVHD).

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Bone Marrow Failure Immunodeficiencies Histiocytosis Sickle Cell Disease Beta Thalassemia Inborn Errors of Metabolism	Drug: Full Intensity with TBI Drug: Full Intensity Drug: Reduced Intensity Drug: Reduced Intensity (Fanconi)	Phase 2

Detailed Description

The selection of CD34+ cells is associated with the simultaneous depletion of T cells that are responsible for severe acute and chronic graft versus host disease (GVHD). Successful engraftment is reported in adult patients with malignant and non-malignant disease who received CD34+ selected stem cells from HLA-matched or mismatched mobilized peripheral blood (PBSC) or bone marrow.

Study Design:

Selected patients defined in the eligibility criteria will enrolled on this study. Patients will receive one of either full intensity or reduced intensity regimen based on the patient's disease status, organ function and performance and determined by the PI and will have peripheral blood undergo CD34 selection.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CD34+Stem Cell Selection for Patients Receiving Partially Matched Family or Matched Unrelated Adult Donor Allogeneic Stem Cell Transplantations for Malignant and Non-Malignant Disease

Study Start Date :

Sep 1, 2011

Actual Primary Completion Date :

Nov 1, 2017

Actual Study Completion Date :

Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Thiotepa/Cyclophosphamide/ATG Full intensity with TBI	Drug: Full Intensity with TBI Patients will start their pre-conditioning regimen on Day -8. Fractionated TBI will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5, -4, Cyclophosphamide on Days -3, -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only. Other Names: ThioTepa Cytoxan Atgam
Experimental: Busulfan/Melphalan/ATG Full intensity without TBI	Drug: Full Intensity Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with stem cell infusion on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only. Other Names: Myleran Alkeran Atgam
Experimental: Busulfan/Fludarabine/Alemtuzumab Reduced Intensity Chemotherapy	Drug: Reduced Intensity Patients will start their GVHD prophylaxis with Tacrolimus on Day -9. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only. Other Names: Fludara Myleran Campath
Experimental: Fludarabine/Cyclophosphamide/ATG Reduced Intensity Chemotherapy for Fanconi Anemia	Drug: Reduced Intensity (Fanconi) Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and antithymocyte globulin (horse) on Days -5, -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only. Other Names: Fludara Cytoxan Atgam

Outcome Measures

Primary Outcome Measures

The safety CD34+ stem cell selection [100 days]
serious adverse events will be monitored post transplant to determine if there is an increase vs. historical data related to the CD34+ selection

Secondary Outcome Measures

Immune reconstitution (T, B, DC) following CD34+ selection [3 years]
immune subsets will be drawn post transplant to determine the rate of reconstitution post CD34+ transplant to determine if this process increases or decreases the reconstitution time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adequate renal function defined as:Serum creatinine <1.5 x normal, or Creatinine clearance or radioisotope GFR >60 ml/min/m2 or an equivalent GFR as determined by the institutional normal range.
Adequate liver function defined as:Total bilirubin <1.5 x normal, or SGOT (AST) or SGPT (ALT) <3.0 x normal
Adequate cardiac function defined as:Shortening fraction >27% by echocardiogram, or Ejection fraction of >47% by radionucleotide angiogram or echocardiogram.
Adequate pulmonary function defined as:Uncorrected DLCO >50% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air.

Eligibility for Reduced Intensity Regimen:

Adequate renal function defined as:Serum creatinine 2.0 x normal, or creatinine clearance or radioisotope GFR > 40 ml/min/m2 or an equivalent GFR as determined by the institutional normal range.
Adequate liver function defined as:Total bilirubin < 2.5 x normal; or SGOT (AST) or SGPT (ALT) < 5.0 x normal.
Adequate cardiac function defined as:Shortening fraction of >25% by echocardiogram, or Ejection fraction of >40% by radionuclide angiogram or echocardiogram.
Adequate pulmonary function defined as:DLCO >35% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% in room air.

Exclusion Criteria:

Pregnancy/Breast Feeding: Females who are pregnant or breast-feeding are not eligible.
Infection: Patients with documented uncontrolled infection at the time of study entry are not eligible.