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

Fanconi Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01019876
• Other study ID #: AAAB0170
• Secondary ID: CHNY-01-509
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: November 23, 2009
• Last updated: October 18, 2011
• Start date: June 2002
• Est. completion date: May 2013

Study information

• Verified date: October 2011
• Source: Columbia University
• Contact: James Garvin, MD, PhD
• Phone: 212 305 5872
• Email: jhg1[@]columbia.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 2013
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Marrow Failure
• Fanconi Anemia
• Fanconi Syndrome
• Immunologic Deficiency Syndromes
• Osteopetrosis
• Pancytopenia
• Severe Combined Immunodeficiency

Intervention

Drug:
• Fludarabine
Fludarabine/Busulfan/Alemtuzumab
• Cyclophosphamide
Cyclophosphamide/Fludarabine/TMG
• Cyclophosphamide 40
Cyclophosphamide/Fludarabine/ATG/TBI
• Cyclophosphamide 30
Cyclophosphamide /Fludarabine/TMG

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Day 30, Day 60, Day 100, 1 year, 2 years	Yes
Secondary	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.		Day 30, Day 60, Day 100, 1 year	Yes
Secondary	To measure immune reconstitution following a Flu/CY or Bu/Flu based conditioning regimen and AlloSCT in patients with selected non-malignant diseases.		Day 30, Day 60, Day 100, 1 year	Yes
Secondary	To estimate the incidence and severity of GVHD following a Flu/Cy or Bu/Flu based conditioning regimen		Day 30, Day 60, Day 100, 1 year	Yes
Secondary	To determine metabolic/immune (gene/protein) reconstitution by standard biochemical/PCR assays in patients		Day 30, Day 60, Day 100, 1 year	Yes

External Links

•   Click on "Morgan Stanley Children's Hospital" and then "Clinical Services" and then "Blood & Marrow Transplantation"