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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Columbia University.
Recruitment status was  Recruiting
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov 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
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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • To determine metabolic/immune (gene/protein) reconstitution by standard biochemical/PCR assays in patients [ Time Frame: Day 30, Day 60, Day 100, 1 year ] [ Designated as safety issue: Yes ]

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
Genders Eligible for Study:   Both
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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01019876

Contact: James Garvin, MD, PhD 212 305 5872 jhg1@columbia.edu
Contact: William A Kim, Ph.D. 212-305-7213 billkim@columbia.edu

United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: James Garvin, MD, PhD    212-305-5872    jhg1@columbia.edu   
Contact: William A Kim, PhD    212-305-7213    billkim@columbia.edu   
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
ClinicalTrials.gov Identifier: NCT01019876     History of Changes
Other Study ID Numbers: AAAB0170  CHNY-01-509 
Study First Received: November 23, 2009
Last Updated: October 18, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Bone marrow Failure

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

ClinicalTrials.gov processed this record on May 24, 2016