Immunoablative Mini Transplant (Hematopoietic Peripheral Blood Stem Cell Transplant [HPBSC]) - Full Text View

Sponsor:	Children's Memorial Hospital
Information provided by:	Children's Memorial Hospital
ClinicalTrials.gov Identifier:	NCT00179764

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	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Immunoablative Protocol for Allogeneic Related and Unrelated Hematopoietic Peripheral Blood Stem Cell Transplant (HPBSC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Melanoma

Drug Information available for: Busulfan

U.S. FDA Resources

Further study details as provided by Children's Memorial Hospital:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Immunoablative conditioning chemotherapy regimen, followed by transplantation of peripheral blood stem cells.

Pharmacokinetics of once-a-day dosing of intravenous busulfan as a 3-hour infusion

Detailed Description:

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.

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00179764

Contacts

Contact: Morris Kletzel, MD	773-880-4562	mkletzel@northwestern.edu
Contact: Terriss Conterato	773-880-8153	TConterato@childrensmemorial.org

Locations

United States, Illinois
Children's Memorial Hospital	Recruiting
Chicago, Illinois, United States, 60614
Principal Investigator: Morris Kletzel, M.D.

Sponsors and Collaborators

Children's Memorial Hospital

Investigators

Principal Investigator:

Morris Kletzel, M.D.

Children's Memorial Hospital

More Information

No publications provided

Responsible Party:	Children's Memorial Hospital ( Morris Kletzel, MD )
Study ID Numbers:	BMT 0300 Mini
Study First Received:	September 10, 2005
Last Updated:	August 26, 2008
ClinicalTrials.gov Identifier:	NCT00179764 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Children's Memorial Hospital:

Patients with recurrent solid tumors
Patients with malignant melanoma
Patients with hematological malignancies
Acute lymphoblastic leukemia (ALL)

Additional relevant MeSH terms:

Leukemia, Lymphoid
Molecular Mechanisms of Pharmacological Action
Hematologic Neoplasms
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Melanoma
Leukemia
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Alkylating Agents
Immunoproliferative Disorders

Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Leukemia, Myeloid
Immunosuppressive Agents
Pharmacologic Actions
Neuroendocrine Tumors
Lymphatic Diseases
Neuroectodermal Tumors
Neoplasms
Busulfan
Myeloablative Agonists
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

ClinicalTrials.gov processed this record on February 08, 2010