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Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases

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ClinicalTrials.gov Identifier: NCT01019876
Recruitment Status : Unknown
Verified October 2011 by Columbia University.
Recruitment status was:  Recruiting
First Posted : November 25, 2009
Last Update Posted : October 19, 2011
Sponsor:
Information provided by (Responsible Party):
Columbia University

Tracking Information
First Submitted Date  ICMJE November 23, 2009
First Posted Date  ICMJE November 25, 2009
Last Update Posted Date October 19, 2011
Study Start Date  ICMJE June 2002
Estimated Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2011)
This study is to determine the toxicity of administering a fludarabine/cyclophosphamide (Flu/CY) or busulfan (Bu)/Flu based conditioning regimen followed by allogeneic stem cell transplant. [ Time Frame: Day 30, Day 60, Day 100, 1 year, 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 23, 2009)
This study is to determine the toxicity of administering a fludarabine/cyclophosphamide (Flu/CY) or busulfan (Bu)/Flu based conditioning regimen followed by allogeneic stem cell transplant. [ Time Frame: 10 years ]
Change History Complete list of historical versions of study NCT01019876 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2011)
  • To determine the risk of disease progression (including neuropsychological deterioration in patients with metabolic non-malignant diseases) following a Flu/CY or Bu/Flu based conditioning regimen. [ Time Frame: Day 30, Day 60, Day 100, 1 year ]
  • To measure immune reconstitution following a Flu/CY or Bu/Flu based conditioning regimen and AlloSCT in patients with selected non-malignant diseases. [ Time Frame: Day 30, Day 60, Day 100, 1 year ]
  • To estimate the incidence and severity of GVHD following a Flu/Cy or Bu/Flu based conditioning regimen [ Time Frame: Day 30, Day 60, Day 100, 1 year ]
  • To determine metabolic/immune (gene/protein) reconstitution by standard biochemical/PCR assays in patients [ Time Frame: Day 30, Day 60, Day 100, 1 year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2009)
  • To determine the risk of disease progression (including neuropsychological deterioration in patients with metabolic non-malignant diseases) following a Flu/CY or Bu/Flu based conditioning regimen. [ Time Frame: 10 years ]
  • To measure immune reconstitution following a Flu/CY or Bu/Flu based conditioning regimen and AlloSCT in patients with selected non-malignant diseases. [ Time Frame: 10 years ]
  • To estimate the incidence and severity of GVHD following a Flu/Cy or Bu/Flu based conditioning regimen [ Time Frame: 10 years ]
  • To determine metabolic/immune (gene/protein) reconstitution by standard biochemical/PCR assays in patients [ Time Frame: 10 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
Official Title  ICMJE Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases
Brief Summary Reduced intensity conditioning followed by allogeneic stem cell transplantation will result in mixed/complete donor chimerism and potentially alter the natural history and outcome of patients with non-malignant diseases.
Detailed Description This study is to determine the toxicity of administering a fludarabine/cyclophosphamide (Flu/CY) or busulfan (Bu)/Flu based conditioning regimen followed by allogeneic stem cell transplant (AlloSCT) in patients with non-malignant diseases.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Bone Marrow Failure
  • Osteopetrosis
  • Fanconi Anemia
  • Severe Combined Immunodeficiency
Intervention  ICMJE
  • Drug: Fludarabine
    Fludarabine/Busulfan/Alemtuzumab
  • Drug: Cyclophosphamide
    Cyclophosphamide/Fludarabine/TMG
  • Drug: Cyclophosphamide 40
    Cyclophosphamide/Fludarabine/ATG/TBI
    Other Name: Cyclophosphamide
  • Drug: Cyclophosphamide 30
    Cyclophosphamide /Fludarabine/TMG
    Other Name: Cyclophosphamide
Study Arms  ICMJE
  • Experimental: Fludarabine
    Intervention: Drug: Fludarabine
  • Experimental: Cyclohosphamide 200
    Intervention: Drug: Cyclophosphamide
  • Experimental: Cyclophosphamide 40
    Intervention: Drug: Cyclophosphamide 40
  • Experimental: Cyclophosphamide 30
    Intervention: Drug: Cyclophosphamide 30
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 23, 2009)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2013
Estimated Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Patients must meet the eligibility criteria for organ function regardless of diagnosis:

    • Age < 30 or = 30 years of age
    • Adequate renal function defined as serum creatinine < or = 1.5 x normal, or creatinine clearance or radioisotope GFR > or =40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
  • Adequate liver function defined as SGOT (AST) or SGPT (ALT) < 5.0 x normal
  • Adequate cardiac function defined as shortening fraction of > or = 28% by echocardiogram, or ejection fraction of > or = 48% by radionuclide angiogram or echocardiogram
  • Adequate pulmonary function defined as asymptomatic or, if symptomatic, DLCO >45% of predicted (corrected for hemoglobin level). If unable to obtain pulmonary function test, O2 saturation >85% in room air.

Bone Marrow Failure Syndromes

Patients with the following diagnoses are eligible:

Severe Aplastic Anemia:

  • Hypocellular bone marrow biopsy (<25% cellularity) and 2/3 of the following (at diagnosis or nadir):
  • Absolute Neutrophil Count (ANC) <200/mm3,
  • Platelets <20,000/mm3
  • Reticulocyte count <60,000/mm3

Fanconi Anemia:

  • Abnormal clastogenic studies (all patients)
  • Severe Congenital Neutropenia (Kostmann's Syndrome)
  • Amegakaryocytic Thrombocytopenia
  • Severe thrombocytopenia (< or =20,000/mm3) at diagnosis
  • Severe depletion of megakaryocytes on bone marrow aspirate (< or =25% normal)

Diamond-Blackfan Anemia:

  • Corticosteroid dependent for > 6 months OR Transfusion dependent OR refractory acquired pure red cell aplasia.
  • Infantile Osteopetrosis
  • Schwachman-Diamond Syndrome
  • Dyskeratosis Congenita

Other bone marrow failure syndromes at discretion of co-principal investigators

  • Immunodeficiencies
  • SCIDS, all subtypes
  • Combined Immunodeficiency Syndrome
  • Wiskott-Aldrich Syndrome
  • Chronic Granulomatous Disease
  • Chediak-Higashi Syndrome
  • Leukocyte Adhesion Deficiency
  • Other immunodeficiencies at discretion of co-principal investigators
  • Inborn Errors of Metabolism (IEOM)

Transplant is recommended for the following disorders:

  • Hurler syndrome (alpha-L-iduronidase deficiency, MPS-I), preferably before age 24 months
  • Maroteaux-Lamy syndrome (galactosamine-4-sulfatase deficiency,MPSVI)
  • Sly syndrome (beta-glucuronidase deficiency, MPS-VII)
  • Globoid cell leukodystrophy (galactocerebrosidase deficiency), with careful attention to neurologic status in the infantile form
  • Metachromatic leukodystrophy (arylsulfatase A deficiency),juvenile or adult onset form; late infantile MLD only if pre-symptomatic
  • Childhood-onset X-linked adrenoleukodystrophy (X-ALD), at initial signs of neuropsychological deterioration, with dietary modification prior to transplant
  • Fucosidosis (fucosidase deficiency)
  • Mannosidosis
  • Aspartylglucosaminuria
  • Niemann-Pick Disease Type B (acid sphingomyelinase deficiency) Other diagnoses may be considered at the discretion of the co-principal investigators
  • For X-ALD patients greater than 5 years of age, IQ >80 is required. For other patients greater than 5 years of age, IQ > 70 is required.
  • For Gaucher disease (glucocerebrosidase deficiency) Type I (non-neuropathic), the primary therapy is enzyme replacement, but allogeneic stem cell transplant has been used effectively.
  • Histiocytoses

    • Hemophagocytic Lymphohistiocytosis (HLH)
    • Familial Erythrophagocytic Lymphohistiocytosis
    • Langerhans Cell Histiocytosis Patients with multi-system disease whose initial disease is stable or progressive after minimum 6 weeks of appropriate therapy, OR Patients with recurrent multi-system disease.
    • Malignant Histiocytosis
  • Other non-malignant diseases not listed above may be eligible if deemed appropriate by the co-principal investigators.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01019876
Other Study ID Numbers  ICMJE AAAB0170
CHNY-01-509 ( Other Identifier: CU )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: James Garvin, MD. PhD Columbia University
PRS Account Columbia University
Verification Date October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP