Immunoablative Mini Transplant (Hematopoietic Peripheral Blood Stem Cell Transplant [HPBSC])
Recruitment status was Recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Tumors Malignant Melanoma Hematological Malignancies Myelogenous Leukemia, Chronic Leukemia, Lymphoblastic, Acute |
Procedure: Immunoablative Hematopoietic PBSC Transplant Procedure: Busulfan pharmacokinetics Radiation: CNS prophylaxis radiation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Immunoablative Protocol for Allogeneic Related and Unrelated Hematopoietic Peripheral Blood Stem Cell Transplant (HPBSC) |
- Evaluate the morbidity and mortality of matched related and unrelated hematopoietic progenitor cell (HPC) transplantation at Children's Memorial Hospital using high dose CD34+ rich HPCs after a reduced intensity conditioning regimen. [ Time Frame: To study end ] [ Designated as safety issue: Yes ]
- Determine the toxicity of a reduced intensity conditioning regimen consisting of Fludarabine and Busulfan. [ Time Frame: To study end ] [ Designated as safety issue: Yes ]
- Validate the pharmacokinetics of once-a-day dosing of intravenous Busulfan given as a 3-hour infusion, using a limited number of samples. [ Time Frame: To study end ] [ Designated as safety issue: No ]
- Assess chimeric engraftment utilizing this regimen in malignant and non-malignant disorders. [ Time Frame: To study end ] [ Designated as safety issue: No ]
- Assess the relapse rate of patients transplanted with this reduced intensity regimen. [ Time Frame: To study end ] [ Designated as safety issue: No ]
- 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. [ Time Frame: To study end ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 100 |
| Study Start Date: | March 2000 |
| Estimated Study Completion Date: | March 2012 |
| Estimated Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
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Procedure: Immunoablative Hematopoietic PBSC Transplant
- Patients diagnosed with ALL over 1 year of age and without prior CNS disease will receive CNS prophylaxis radiation to the whole brain prior to transplant.
- Patients diagnosed with ALL with prior CNS disease over the age of 1 year will be treated with prophylaxis radiation to the whole brain and spine prior to 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.
Eligibility| Ages Eligible for Study: | up to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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)
- First remission high-risk ALL (Ph+ with initial high white blood cell [WBC]; t (4-11) in infants less than 1 year and CALLA negative)
- Second or subsequent remission ALL or isolated extramedullary disease on or off therapy.
Acute non-lymphocytic leukemia (ANLL)
- Patients with ANLL in first remission who have a matched sibling donor.
- ANLL in second remission, or patients who only achieve an initial partial remission < 15% blasts, or early relapse.
- 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:
- Wiskott-Aldrich syndrome.
- Severe combined immunodeficiency variants that require ablation.
- Hyper-IGM syndrome.
- Other immune deficiencies after approval from the medical director.
- 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:
- Adequate renal function: serum creatinine < 2 x normal, or creatinine clearance calculated by Schwartz formula, of glomerular filtration rate (GFR) > 40 ml/min/1.73m2, or an equivalent GFR as determined by the institutional normal range.
- Adequate liver function: total bilirubin </= 2 x normal; and SGOT (AST) or SGPT (ALT) </= 4 x normal.
- Adequate cardiac function: shortening fraction of > 24% by echocardiogram, or ejection fraction of > 30% by radionuclide angiogram.
- Adequate pulmonary function: DLCO, FEV1 / FVC > 30% by pulmonary function test. For children who are uncooperative for pulmonary function tests and have no evidence of dyspnea at rest or exercise intolerance, pulse oximetry > 94% on room air is considered acceptable.
- Performance status: Lansky >/= 60% for children </= 16 years of age; or Karnofsky > 60% status for those > 16 years of age.
Exclusion Criteria:
- Patients who are pregnant
- Inability to find a suitable donor for the patient
- Patient is HIV-positive
- Patient has active Hepatitis B
- Disease progression or relapse prior to HPC infusion
Contacts and Locations| Contact: Morris Kletzel, MD | 773-880-4562 | mkletzel@northwestern.edu |
| Contact: Terriss Conterato | 773-880-8153 | TConterato@childrensmemorial.org |
| United States, Illinois | |
| Children's Memorial Hospital | Recruiting |
| Chicago, Illinois, United States, 60614 | |
| Principal Investigator: Morris Kletzel, M.D. | |
| Principal Investigator: | Morris Kletzel, M.D. | Ann & Robert H Lurie Children's Hospital of Chicago |
More Information
No publications provided
| Responsible Party: | Morris Kletzel, MD, Children's Memorial Hospital |
| ClinicalTrials.gov Identifier: | NCT00179764 History of Changes |
| Other Study ID Numbers: | BMT 0300 Mini |
| Study First Received: | September 10, 2005 |
| Last Updated: | October 7, 2010 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Ann & Robert H Lurie Children's Hospital of Chicago:
|
Patients with recurrent solid tumors Patients with malignant melanoma Patients with hematological malignancies Acute lymphoblastic leukemia (ALL) Acute myelogenous leukemia (AML) |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Melanoma Hematologic Neoplasms Chronic Disease Neoplasms by Histologic Type Leukemia, Lymphoid Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Myeloproliferative Disorders |
Bone Marrow Diseases Hematologic Diseases Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nevi and Melanomas Neoplasms by Site Disease Attributes Pathologic Processes Busulfan Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013