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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 November 2024
• 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: September 2002
• Target sample size: 38
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT01019876
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• 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 glomerular filtration rate (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 serum glutamic oxaloacetic transaminase
(SGOT)(Aspartate transaminase (AST)) or serum glutamic-pyruvic transaminase (SGPT)
(alanine aminotransferase (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, carbon
monoxide diffusing capacity test (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 All BM failure
patients must have BM bx within 2 weeks prior to starting therapy to confirm disease
status

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

Transplant is not recommended for Hunter syndrome (iduronate sulfatase deficiency),
Sanfilippo syndrome Type A (heparan N-sulfatase deficiency), Sanfilippo syndrome Type B
(-N-acetyl-transferase deficiency), Sanfilippo syndrome Type C (-acetyltransferase
deficiency), Sanfilippo syndrome Type D (-acetylglucosamine-6-sulfatase deficiency),
Morquio syndrome (galactose-6-sulfatase deficiency); or Niemann-Pick disease Type A or C.

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 patients less than 5 years of age, the developmental quotient or clinical
neurodevelopmental examination should demonstrate potential for stabilization at a level
of functioning where continuous life support (e.g. mechanical ventilation) would not be
predicted to be required in the year following transplantation.

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

- All histiocytic patients must have BM bx within 2 weeks prior to starting therapy to
confirm disease status

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: All

Health Condition(s) or Problem(s) studied

Osteopetrosis

Fanconi Anemia

Bone Marrow Failure

Severe Combined Immunodeficiency

Intervention(s)

Drug: Fludarabine

Drug: Horse Anti-thymocyte Globulin

Drug: Alemtuzumab

Drug: Busulfan

Drug: Cyclophosphamide

Drug: Rabbit Anti-thymocyte Globulin

Primary Outcome(s)

Number of participants with Adverse Events [Time Frame: Up to 2 years]

Secondary Outcome(s)

Risk of disease progression [Time Frame: Up to 1 year]

Incidence of graft versus host disease (GVHD) [Time Frame: Up to 1 year]

Immune reconstitution [Time Frame: Up to 1 year]

Metabolic/Immune reconstitution [Time Frame: Up to 1 year]

Secondary ID(s)

AAAB0170

CHNY-01-509

Source(s) of Monetary Support

Please refer to primary and secondary sponsors