Unrelated Donor Transplant for Malignant and Non-Malignant Disorders

Sponsor

Columbia University (Other)

Overall Status

Terminated

CT.gov ID

NCT01050439

Collaborator

(none)

Enrollment

Location

Arm

101

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Unrelated matched donor (cord blood, bone marrow or peripheral blood) allogeneic stem cell transplantation (UDAlloSCT) with either myeloablative or reduced intensity conditioning will be well tolerated and result in a high degree of engraftment in patients with selected malignant and non malignant disorders.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Bone Marrow Failure Syndromes Immunodeficiencies Histiocytosis	Procedure: UDAlloSCT Other: Therapy	Phase 2

Detailed Description

This is a non-randomized study to determine the tolerability and degree of engraftment of unrelated matched donor allogeneic stem cell transplantation with either myeloablative or reduced intensity conditioning in patients with selected malignant and non malignant disorders. Patients will receive one of either full intensity or reduced intensity regimen based on the patient's disease status, organ function and performance and determined by the PI.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Unrelated Donor Stem Cell Transplant for Patients With Malignant and Non-Malignant Disorders

Study Start Date :

Nov 1, 2002

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UDAlloSCT + Therapy This is a non-randomized study to test the safety and response of unrelated matched donor allogeneic stem cell transplantation (UDAlloSCT) with either myleoablative (full intensity) or reduced intensity conditioning therapy in patients with selected malignant and non-malignant disorders. UDAlloSCT has been performed in both adults and children as an alternative transplant for patients who lack and HLA-matched family donor in both malignant and non-malignant disease with varying degrees of response.	Procedure: UDAlloSCT unrelated matched donor allogeneic stem cell transplantation (UDAlloSCT) Other: Therapy Full Intensity Therapy (myeloablative) (TBI + Thiotepa + Cyc) OR Reduced Intensity Therapy (Fludarabine, Busulfan, and Alemutuzumab (FBA))

Arm

Intervention/Treatment

Experimental: UDAlloSCT + Therapy

This is a non-randomized study to test the safety and response of unrelated matched donor allogeneic stem cell transplantation (UDAlloSCT) with either myleoablative (full intensity) or reduced intensity conditioning therapy in patients with selected malignant and non-malignant disorders. UDAlloSCT has been performed in both adults and children as an alternative transplant for patients who lack and HLA-matched family donor in both malignant and non-malignant disease with varying degrees of response.

Procedure: UDAlloSCT

unrelated matched donor allogeneic stem cell transplantation (UDAlloSCT)

Other: Therapy

Full Intensity Therapy (myeloablative) (TBI + Thiotepa + Cyc) OR Reduced Intensity Therapy (Fludarabine, Busulfan, and Alemutuzumab (FBA))

Outcome Measures

Primary Outcome Measures

Incidence of toxicity related to myeloablative therapy [Up to 10 years from start of study]
To determine the safety and toxicity of myeloablative therapy (TBI + Melphalan) and unrelated donor alloSCT in selected patients with malignant and non-malignant disorders.

Secondary Outcome Measures

Incidence of toxicity related to reduced intensity therapy [Up to 10 years from start of study]
To determine the safety and toxicity of reduced intensity therapy (Fludarabine, Busulfan, and Alemtuzumab (FBA) and unrelated donor alloSCT in selected patients with malignant and non malignant disorders
Percentage of donor chimerism [Up to 10 years from start of study]
To quantitate the percentage of donor chimerism following both myeloablative and reduced intensity conditioning and unrelated donor alloSCT in selected patients with malignant and non-malignant disorders.
Prevalence of progression free survival [Up to 10 years from start of study]
To estimate the progression free survival (PFS), if applicable, event free survival (EFS) and overall survival (OS) following unrelated donor alloSCT in selected patients with malignant and non malignant disorders.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adequate renal function defined as: serum creatinine 2.0 x normal, or creatinine clearance or radioisotope GFR > 40 ml/min/m2 or > 40 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.
Adequate liver function defined as: total bilirubin < 2.5 x normal; or SGOT (AST) or SGPT (ALT) < 5.0 x normal.
Adequate cardiac function defined as: shortening fraction of > 25% by echocardiogram, or ejection fraction of > 40% by radionuclide angiogram or echocardiogram.
Adequate pulmonary function defined as: DLCO > 35% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% in room air.
Diseases:
CML (CP, AP or BC)
AML/MDS/JCML
ALL
Lymphoma (Hodgkin's and non-Hodgkin's)
Non-malignant disorders
Bone Marrow Failure Syndromes: Patients with the following diagnoses are eligible:
Severe Aplastic Anemia:
Fanconi Anemia
Severe Congenital Neutropenia (Kostmann's Syndrome)
Amegakaryocytic Thrombocytopenia
Diamond-Blackfan Anemia
Infantile Osteopetrosis
Schwachman-Diamond Syndrome
Dyskeratosis Congenita
Other bone marrow failure syndromes at discretion of Principal Investigator
Immunodeficiencies:
SCIDS, all subtypes
Combined Immunodeficiency Syndrome
Wiskott-Aldrich syndrome
Chronic Granulomatous Disease
Chediak-Higashi Syndrome
Leukocyte Adhesion Deficiency
Other immunodeficiencies at discretion of Principal Investigator
Inborn Errors of Metabolism (IEOM):
Transplant is recommended for the following disorders: Hurler syndrome (L-iduronidase deficiency, MPS-I), Maroteaux-Lamy syndrome (galactosamine-4-sulfatase deficiency, MP VI), Sly syndrome (glucuronidase deficiency, MPS-VII), Globoid cell Leukodystrophy (galactocerebrosidasedeficiency), Metachromatic leukodystrophy (arylsulfatase A deficiency), Childhood-onset X-linked adrenoleukodystrophy (X-ALD), Fucosidosis (fucosidase deficiency), Mannosidosis, Aspartylglucosaminuria, Niemann-Pick Disease Type B (acid sphingomyelinase deficiency), Gaucher disease (glucocerebrosidase deficiency) Type I (non neuropathic), Other diagnoses may be considered at the discretion of the Principal Investigator
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.
Histiocytosis:
Hemophagocytic Lymphohistiocytosis (HLH)
Familial Erythrophagocytic Lymphohistiocytosis
Langerhans Cell Histiocytosis
Malignant Histiocytosis
Other Malignant and non-malignant diseases: Other malignant and non-malignant diseases not listed above may be eligible if deemed appropriate by the Principal Investigator.