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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2011 by Columbia University.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
Columbia University Identifier:
First received: November 23, 2009
Last updated: October 18, 2011
Last verified: October 2011
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.

Condition Intervention Phase
Bone Marrow Failure Osteopetrosis Fanconi Anemia Severe Combined Immunodeficiency Drug: Fludarabine Drug: Cyclophosphamide Drug: Cyclophosphamide 40 Drug: Cyclophosphamide 30 Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases

Resource links provided by NLM:

Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 50
Study Start Date: June 2002
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine Drug: Fludarabine
Experimental: Cyclohosphamide 200 Drug: Cyclophosphamide
Experimental: Cyclophosphamide 40 Drug: Cyclophosphamide 40
Other Name: Cyclophosphamide
Experimental: Cyclophosphamide 30 Drug: Cyclophosphamide 30
Cyclophosphamide /Fludarabine/TMG
Other Name: Cyclophosphamide

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.

Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01019876

Contact: James Garvin, MD, PhD 212 305 5872
Contact: William A Kim, Ph.D. 212-305-7213

United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: James Garvin, MD, PhD    212-305-5872   
Contact: William A Kim, PhD    212-305-7213   
Principal Investigator: James Garvin, MD, PhD         
Sponsors and Collaborators
Columbia University
Principal Investigator: James Garvin, MD. PhD Columbia University
  More Information

Additional Information:
Responsible Party: Columbia University Identifier: NCT01019876     History of Changes
Other Study ID Numbers: AAAB0170
CHNY-01-509 ( Other Identifier: CU )
Study First Received: November 23, 2009
Last Updated: October 18, 2011

Keywords provided by Columbia University:
Bone marrow Failure

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Fanconi Anemia
Fanconi Syndrome
Severe Combined Immunodeficiency
Immune System Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Infant, Newborn, Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Fludarabine phosphate
Immunosuppressive Agents processed this record on September 19, 2017