Immunoablative Mini Transplant (Hematopoietic Peripheral Blood Stem Cell Transplant [HPBSC])

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor:
Information provided by (Responsible Party):
Reggie E Duerst, MD, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier:
NCT00179764
First received: September 10, 2005
Last updated: January 30, 2014
Last verified: January 2014
  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)

Resource links provided by NLM:


Further study details as provided by Ann & Robert H Lurie Children's Hospital of Chicago:

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 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Immunoablative Hematopoietic PBSC Transplant
    Immunoablative conditioning chemotherapy regimen, followed by transplantation of peripheral blood stem cells on Day 0 of the conditioning regimen.
    Procedure: Busulfan pharmacokinetics
    Pharmacokinetics of once-a-day dosing of intravenous busulfan as a 3-hour infusion
    Radiation: CNS prophylaxis radiation
    • 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.
Detailed Description:

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
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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Reggie Duerst, MD 312-227-4090 rduerst@luriechildrens.org
Contact: Colleen Rosen 312-227-4870 crosen@luriechildrens.org

Locations
United States, Illinois
Children's Memorial Hospital Recruiting
Chicago, Illinois, United States, 60614
Principal Investigator: Morris Kletzel, M.D.         
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Investigators
Principal Investigator: Morris Kletzel, M.D. Ann & Robert H Lurie Children's Hospital of Chicago
  More Information

No publications provided

Responsible Party: Reggie E Duerst, MD, MD, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier: NCT00179764     History of Changes
Other Study ID Numbers: BMT 0300 Mini
Study First Received: September 10, 2005
Last Updated: January 30, 2014
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:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms
Melanoma
Hematologic Neoplasms
Chronic Disease
Neoplasms by Histologic Type
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
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Busulfan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014