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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01019876
• Date of registration: 23/11/2009
• Prospective Registration: No
• Primary sponsor: Columbia University
• Public title: Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
• Scientific title: Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases
• Date of first enrolment: June 2002
• Target sample size: 50
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01019876
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: James Garvin, MD, PhD

• Name: James Garvin, MD, PhD

• Name: James Garvin, MD. PhD
• Affiliation: Columbia University

Key inclusion & exclusion criteria

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.



Age minimum: N/A
Age maximum: 30 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Severe Combined Immunodeficiency

Bone Marrow Failure

Fanconi Anemia

Osteopetrosis

Intervention(s)

Drug: Cyclophosphamide 30

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: Cyclophosphamide 40

Primary Outcome(s)

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(s)

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

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 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 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]

Secondary ID(s)

CHNY-01-509

AAAB0170

Source(s) of Monetary Support

Please refer to primary and secondary sponsors