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Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00744692
Recruitment Status : Completed
First Posted : September 1, 2008
Results First Posted : August 13, 2014
Last Update Posted : August 13, 2014
Sponsor:
Information provided by (Responsible Party):
Duke University

Study Description
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Brief Summary:
The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

Condition or disease Intervention/treatment Phase
Non Malignant Disorders Immunodeficiencies Congenital Marrow Failures Hemoglobinopathies Inborn Errors of Metabolism Sickle Cell Thalassemia Lysosomal Storage Disease Biological: Unrelated Umbilical Cord Blood Transplant Drug: Reduced Intensity Conditioning Phase 1

Detailed Description:

Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

The secondary objectives are:

  • To describe the pace of neutrophil and platelet recovery
  • To evaluate the pace of immune reconstitution.
  • To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
  • To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
  • To describe the incidence of grade 3-4 organ toxicity
  • To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
  • To evaluate the incidence of late graft failures at 2 years post-transplant
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation
Study Start Date : October 2008
Actual Primary Completion Date : December 2012
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: RIC Cord Blood Transplant
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
 Biological: Unrelated Umbilical Cord Blood Transplant
Reduced Intensity Conditioning for unrelated umbilical cord blood transplant

Drug: Reduced Intensity Conditioning
Other Names:
  • Campath
  • Hydroxyurea
  • Fludarabine
  • Melphalan
  • Thiotepa


Outcome Measures
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Primary Outcome Measures :
  1. Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders. [ Time Frame: 180 days post transplant ]
    Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders.


Secondary Outcome Measures :
  1. To Describe the Pace of Neutrophil Recovery [ Time Frame: 42 days post transplant ]
    Neutrophil recovery was defined as the first day of an absolute neutrophil count (ANC) more than 500/uL for 3 consecutive days not secondary to granulocyte infusions

  2. To Evaluate the Pace of Immune Reconstitution. [ Time Frame: 1 year post transplant ]
    Immune reconstitution after RIC in UCBT was described. CD4 count is a standard measure of immune reconstitution and is described here. Additional data is available upon request.

  3. To Determine the Overall Survival at day180 Post-transplant [ Time Frame: 180 days ]
    To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis

  4. To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV) [ Time Frame: 100 days post transplant ]
    To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) : measured by cumulative incidence analysis

  5. To Describe the Incidence of Grade 3-4 Organ Toxicity [ Time Frame: 2 years post transplant ]
  6. To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure [ Time Frame: at least 2 years post transplant ]
  7. To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant [ Time Frame: 2 years post transplant ]
  8. To Describe the Pace of Platelet Recovery [ Time Frame: 180 days post transplant ]
    Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions


Eligibility Criteria
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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure syndrome, inborn error of metabolism, or hereditary anemia
  • Appropriately matched related or unrelated umbilical cord blood unit with a cell dose ≥ 3 x 10e7cells/kg
  • Performance score (lansky or karnofsky) greater than or equal to 70
  • Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50 ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26% or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests demonstrating CVC or FEV1/FVC of >60% of predicted for age.)
  • Informed consent
  • Not pregnant or breast feeding
  • Minimum life expectancy of at least 6 months
  • HIV negative
  • No uncontrolled infections at the time of cytoreduction
  • Disease specific inclusion criteria

Exclusion Criteria:

  • Patients with hemoglobinopathies > 3 years of age
  • UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching
  • Available HLA-matched related living donor able to donate without previous UCB donation
  • Allogeneic hematopoietic stem cell transplant within the previous 6 months
  • Any active malignancy, MDS, or any history of malignancy
  • Severe acquired aplastic anemia
  • DLCO < 60% of normal value for age; requirement for supplemental oxygen
  • Uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms)
  • Pregnancy or nursing mother
  • HIV/HTLV seropositive, Hep B surface antigen positive, or HCV RNA positive by PCR
  • Any condition that precludes serial follow-up
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00744692


Locations
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United States, North Carolina
Duke University Medical Center Pediatric Blood and Marrow Transplant Program
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Suhag Parikh, MD Duke Pediatric Blood and Marrow Transplant
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00744692    
Other Study ID Numbers: Pro00008753
First Posted: September 1, 2008    Key Record Dates
Results First Posted: August 13, 2014
Last Update Posted: August 13, 2014
Last Verified: July 2014
Keywords provided by Duke University:
Immunodeficiencies
Congenital Marrow Failures
Hemoglobinopathies
Inborn Errors of Metabolism
SCIDS
Wiskott Aldrich
FEL
HLH
IPEX
LAD
Sickle Cell
Thalassemia
 Omenn's Syndrome
Hurler's Syndrome
MLD
ALD
Sanfilippo
Krabbe
Hunter's syndrome
TaySachs
Diamond Blackfan Anemia
transplant
MPS
Gaucher
Additional relevant MeSH terms:
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Thalassemia
Hemoglobinopathies
Metabolism, Inborn Errors
Lysosomal Storage Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Fludarabine
Melphalan
 Thiotepa
Hydroxyurea
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antisickling Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors