CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant
Chronic Myeloid Leukemia (CML), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS)
About this trial
This is an interventional treatment trial for Chronic Myeloid Leukemia (CML) focused on measuring Unrelated donor transplant, Allogenic Stem Cell Transplant, Adult Bone Marrow Transplant, Pediatric Bone Marrow Transplant, Related donor transplant, Haploidentical donor transplant, Peripheral blood stem cell transplantation, Non-malignant disease, Malignant disease, Bone marrow failure syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia, Diamond-Blackfan Anemia, Schwachman Diamond Syndrome, Primary Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome, Histiocytic Syndrome, Familial Hemophagocytic Lymphocytosis, Lymphohistiocytosis, Macrophage Activation Syndrome, Langerhans Cell Histiocytosis (LCH), Hemoglobinopathies, Reduced-Intensity Conditioning, Sickle Cell Disease, Sickle Cell-beta-thalassemia
Eligibility Criteria
Inclusion Criteria: General Eligibility (All Patients)
- Must be < 22 years of age
- Diagnosed with a malignant disease
- Must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent
- For unrelated donor: A human leukocyte antigen (HLA) 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry
- For related donor: A 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 matched (or partially matched) family donor will be required for study entry
- Adequate renal function
- Adequate liver function
- Adequate cardiac function
- Adequate pulmonary function
Exclusion Criteria:
- Patients with documented uncontrolled infection at the time of study entry are not eligible
- Females who are pregnant or breast feeding at the time of study entry are not eligible
Sites / Locations
- Columbia University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Full intensity with TBI
Full intensity without TBI
Reduced intensity
Patients will start their pre-conditioning regimen on 8 days before scheduled transplant. Fractionated total body irradiation (TBI) will be administered twice daily on the 6th, 7th, and 8th before transplant. Patients will receive Thiotepa on the 4th and 5th day before transplant, Cyclophosphamide on the 2nd and 3rd day before transplant, and Alemtuzumab on the 1st-5th day(s) before transplant. Then the stem cell infusion will be performed (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after transplant, and methylprednisolone will start on day -5.
Patients will start their pre-conditioning regimen 9 days before their scheduled transplant. Patients will receive busulfan twice daily on the 5th-8th day before transplant, and Melphalan on the 2nd-4th days before transplant and Alemtuzumab on the 1st-5th day before transplant. Subjects will then undergo with their stem cell infusion (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System) and GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after their transplant, and methylprednisolone will start on day -5.
Patients will begin tacrolimus 8 days pre-transplant, and then will receive alemtuzumab on the 3rd-7th day pre-transplant; busulfan twice daily on the 5th-8th day pre-transplant; and fludarabine on the 2nd-7th day pre-transplant. Methylprednisolone will start on day -7.The stem cell infusion will be performed (with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus or sirolimus. For patients with a history of hepatic toxicity and/or high-risk for veno-occlusive disease or other liver toxicity post stem cell transplant, melphalan at 70 mg/m2 will be substituted for Busulfan, followed by fludarabine on the 2nd-7th day before transplant and alemtuzumab on the 3rd-7th day before transplant.