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The purpose of this research study is to evaluate the effectiveness of transplantation of high doses of peripheral blood stem cells (stem cells are special cells found in the blood and bone marrow that produce new blood cells) after treatment with non-myeloablative chemotherapy (not toxic to the bone marrow). In addition, this study will assess the side effects of the transplant.
The standard treatment in many disorders of the bone marrow is high dose chemotherapy and whole-body radiation treatment followed by the stem cell transplant. This type of transplant not only suppresses or kills off the immune system, but is very toxic to the bone marrow. This study uses a chemotherapy regimen that will suppress the patient's immune system; however, it is non-myeloablative (not toxic to the bone marrow). It does not use whole-body radiation treatment. This approach can minimize the short- and long-term effects of transplantation. Other studies have shown that using chemotherapy followed by bone marrow transplantation without whole-body radiation can produce similar results as treatment with whole-body radiation.
Patients will be given chemotherapy with Fludarabine and Busulfan prior to the stem cell transplant. This treatment not only destroys diseased cells, but it also kills normal bone marrow cells. Following this experimental treatment, the patient will be given the stem cells through a central venous catheter (tube inserted in a vein). When the healthy stem cells are given to the patient, they will replace the destroyed bone marrow cells and produce new blood cells. The Allogeneic (not one's own) stem cells used in this experimental transplant will be obtained from a related matched donor or from an unrelated matched donor located through the National Marrow Donor Program.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reduced Intensity Conditioning Regimen | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immunoablative Hematopoietic PBSC Transplant | Procedure | Immunoablative conditioning chemotherapy regimen, followed by transplantation of peripheral blood stem cells on Day 0 of the conditioning regimen. |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the morbidity and mortality of matched related and unrelated hematopoietic progenitor cell (HPC) transplantation at Children's Memorial Hospital using high dose CD34+ HPCs after a reduced intensity conditioning regimen. | To study end | |
| Determine the toxicity of a reduced intensity conditioning regimen consisting of Fludarabine and Busulfan. | To study end |
| Measure | Description | Time Frame |
|---|---|---|
| Validate the pharmacokinetics of once-a-day dosing of intravenous Busulfan given as a 3-hour infusion, using a limited number of samples. | To study end | |
| Assess chimeric engraftment utilizing this regimen in malignant and non-malignant disorders. | To study end |
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Inclusion Criteria:
Patients with recurrent solid tumors
Patients with malignant melanoma
Patients with hematological malignancies.
Chronic myelogenous leukemia in chronic or accelerated phase, to include chronic myelomonocytic leukemia (juvenile chronic myelogenous leukemia (JCML) or CMML).
Acute lymphoblastic leukemia (ALL)
Acute non-lymphocytic leukemia (ANLL)
Myelodysplastic syndromes (MDS): refractory anemia (RA), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T) and CMML/JCML.
Selected immunodeficiencies:
Bone marrow failure syndromes (single or multiple hematopoietic lines)
Venous access: A double lumen central vascular access device or its equivalent will be required for all patients entered on the protocol.
Informed consent: The donor and the patient and/or the patient's legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policy approved by the United States (U.S.) Department of Health and Human Services.
Patient organ function requirements:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Morris Kletzel, M.D. | Ann & Robert H Lurie Children's Hospital of Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lurie Children's Hospital | Chicago | Illinois | 60611 | United States |
| Type | Date | Date Unknown |
|---|---|---|
| Release | Sep 22, 2021 | |
| Reset | Oct 19, 2021 |
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| Busulfan pharmacokinetics | Procedure | Pharmacokinetics of once-a-day dosing of intravenous busulfan as a 3-hour infusion |
|
| Central Nervous System (CNS) prophylaxis radiation | Radiation |
|
|
| Assess the relapse rate of patients transplanted with this reduced intensity regimen. | To study end |
| Determine the incidence of acute and chronic Graft vs. Host Disease (GVHD) using prophylaxis with Cyclosporine A and mycophenolate mofetil following this reduced intensity regimen. | To study end |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Sep 22, 2021 | Oct 19, 2021 |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008545 | Melanoma |
| D019337 | Hematologic Neoplasms |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D009720 | Nurse Clinicians |
| ID | Term |
|---|---|
| D000072184 | Nurse Specialists |
| D009726 | Nurses |
| D006282 | Health Personnel |
| D005159 | Health Care Facilities Workforce and Services |
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