Unrelated Donor Transplant for Malignant and Non-Malignant Disorders

Phase 2

Terminated

• Conditions: Leukemia; Bone Marrow Failure Syndromes; Immunodeficiencies; Histiocytosis; Lymphoma
• Interventions: Procedure: UDAlloSCT; Other: Therapy

• Registration Number: NCT01050439
• Lead Sponsor: Columbia University

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.

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 Timeline

• Study Start: 2002-11
• Study First Submitted: 2008-06-03
• Study First Submitted QC: 2010-01-14
• Study First Posted: 2010-01-15
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-14
• Last Update Posted: 2015-04-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 22

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.

Exclusion Criteria

• Women who are pregnant and/or breast feeding are ineligible

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
UDAlloSCT + Therapy	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.
UDAlloSCT + Therapy	UDAlloSCT	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

Columbia University Medical Center; 🇺🇸 New York, New York, United States