Expanded Use of G-CSF Mobilized Donor CD34+ Selected Cells for Allogeneic Transplantation

Study Overview
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Brief Summary
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Allogeneic hematopoietic stem cell transplantation (HSCT) is an established form of treatment for hematological abnormalities. Poor graft function, occurs when there poor donor engraftment. A second infusion of unselected donor hematopoietic stem cells (HSC) can result in improvement, but can potentially increase the incidence of graft versus host disease. Cluster of differentiation 34+ (CD34+) selected stem cells depleted of T-cells is an attractive alternative for treatment of poor graft function as it may be associated with less Graft versus Host Disease (GVHD) and enhanced count recovery. The investigators are using the Miltenyi CliniMACS device and CD34 cell selection reagents for the preparation of allogeneic hematopoietic progenitor cell (HPC) transplants for patients who have had prior stem cell transplants and require a stem cell boost from the original donor.

Detailed Description
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This is a single-arm, open label, single institution, compassionate study which will enroll patients who are marginally engrafted and transfusion and/or growth factors dependent after allogeneic hematopoietic stem cell transplant (HSCT) regardless of the underlying disease for which the transplant was performed. Study subjects will receive a booster infusion of CD34+ cell selected and T-cell depleted G-CSF mobilized apheresis product from the original stem cell donor in order to improve engraftment. The booster infusion will be administered without prior conditioning.

Official Title
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Expanded Use of G-CSF Mobilized Donor CD34+ Selected Cells for Allogeneic Transplantation to Recipients With Limited Donor Engraftment

Conditions
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Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Biological: G-CSF mobilized CD34+ selected cells for transplantation


Participation Criteria
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Eligibility Criteria
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Donor Inclusion Criteria: Donors must be eligible and approved for a hematopoietic stem cell graft according to institutional criteria (related donor) or NMDP criteria (volunteer unrelated donor) Donors must be ≥ 17 years old and ≤ 75 years old Donors must be agreeable to receive G-CSF for CD34 cell mobilization and undergo apheresis for the second donation of peripheral blood mononuclear cells (PBMC) Donor must have adequate peripheral venous catheter access for apheresis or must agree to placement of a central catheter The following laboratory tests/evaluations will be performed for all donors registered in the study. Additional evaluations/studies may also be performed by the site as dictated by the donor's clinical situation or standard practice for monitoring normal donors History and physical examination Automated complete blood count (WBC, red blood cells [RBC], hematocrit, hemoglobin) with differential and platelet counts Serum chemistries panel including electrolytes, glucose, blood urea nitrogen (BUN), alanine aminotransferase (ALT), creatinine, bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH) and albumin. Electrolytes to include sodium, potassium, chloride, carbon dioxide, calcium and magnesium. Infections disease titers by FDA licensed tests for: Cytomegalovirus (CMV) antibody Hepatitis panel (Hepatitis B including HBsAg, HBcAb [immunoglobulin M {IgM} and immunoglobulin G {IgG}]; hepatitis C antibody) HIV 1+2 antibodies Hepatitis C virus (HCV) antibodies Human T-lymphotropic virus (HTLV) I/II antibodies Rapid plasmin reagin (RPR) HIV-1 nucleic acid amplification test (NAT) HCV NAT West Nile virus (WNV) These tests will be obtained, and reported to Emory, within 30 days prior to collection of the CD34+ cell product. Recipient Inclusion Criteria: Only patients who are experiencing life-threatening hematological insufficiency, following an allogeneic hematopoietic stem cell transplant will be enrolled into this study Patient must be age > 17 Must have ≥ 90% donor cells in the unfractionated peripheral blood based on either XY fluorescence in situ hybridization (FISH) or standard short tandem repeats (STR) More than 60 days post allogeneic stem cell transplantation and no reversible etiology found after an allogeneic stem cell transplantation Must meet one of the following criteria: Platelets < 20,000/μl, absolute neutrophil count (ANC) < 500/μl or Transfusion dependent for at least one cell line and/or On growth factor support (G-CSF) without adequate response for 30 days The original HSCT donor must be available, willing, and medically able to undergo G-CSF mobilization and the apheresis procedures Patients must have non-immune mediated graft dysfunction

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: G-CSF mobilized CD34+ selected cells for transplantation|After screening and enrollment, donor will receive mobilization therapy with G-CSF (10 ug/Kg S/C daily x5-6 days) using standard National Marrow Donor Program guidelines. CD34+ cell selection will be performed according to procedures given in CliniMACS Operating Manual and institutional Standard Operating Procedures. If storage after CD34+ selection is necessary, product will be kept in a monitored refrigerator. During storage, leukocyte concentration should not exceed 2 x 108 cells/ml using platelet poor plasma to adjust cell concentration. If donor's plasma is not available, CliniMACS buffer will be used. Cell processing will be performed by personnel trained by Miltenyi on CliniMACS system prior to initiation of clinical product selection. After tests are performed and product passes release criteria, patient will receive final product. No conditioning regimen will be administered prior to cell infusion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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G-CSF, chronic myeloid leukemia, myelodysplastic syndrome, acute myeloid leukemia, CD34+ cell mobilization therapy, graft versus host disease, allogeneic hematopoietic stem cell