Unrelated Donor Transplant for Malignant and Non-Malignant Disorders

This study has been terminated.
(PI left institution)
Sponsor:
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT01050439
First received: June 3, 2008
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Bone Marrow Failure Syndromes
Immunodeficiencies
Histiocytosis
Drug: Myeloablative chemotherapy and TBI
Drug: Myeloablative chemotherapy
Drug: Reduced Intensity Chemoimmunotherapy
Drug: Reduced Intensity for Fanconi Anemia
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Unrelated Donor Stem Cell Transplant for Patients With Malignant and Non-Malignant Disorders

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • To determine the safety and toxicity of myeloablative therapy (TBI + Melphalan) and unrelated donor alloSCT in selected patients with malignant and non-malignant disorders. [ Time Frame: Up to 10 years from start of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 10 years from start of study ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Up to 10 years from start of study ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Up to 10 years from start of study ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: November 2002
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Myeloablative chemotherapy and TBI
    TBI 200cGy BID X 3 DAYS (1200cGy) Thiotepa 5 mg/kg x 2 Days Cyclophosphomide 60 mg/kg x 2 Days Rabbit Antithymocyte Globulin 2 mg/kg x 4 days (total 8 mg/kg)
    Other Names:
    • Cytoxan
    • Atgam
    Drug: Myeloablative chemotherapy
    BUSULFAN 4 mg/kg/day (4 yrs), 3.2 mg/kg/day (> 4 yrs) X 4 DAYS MELPHALAN 45mg/m2 X 3 DAYS (total 135mg/m2) Rabbit Antithymocyte Globulin 2 mg/kg x 4 days (total 8 mg/kg)
    Other Names:
    • Busulfex
    • Rabbit Atgam
    • Alkeran
    Drug: Reduced Intensity Chemoimmunotherapy

    BUSULFAN 4 mg/kg/day (4 yrs), 3.2 mg/kg/day (> 4 yrs) X 4 DAYS FLUDARABINE 30 mg/ m2 X 6 DAYS

    ALEMTUZUMAB 2mg/m2 x 1 day (max 3 mg) 6mg/m2 x 2 days (max 10mg) 20mg/m2 x 2 days (max 30mg)

    Other Names:
    • Busulfex
    • Campath
    • Fludara
    Drug: Reduced Intensity for Fanconi Anemia
    TBI 450 cGy X 1 DAY CYCLOPHOSPHAMIDE 10/mg/kg X 4 DAYS FLUDARABINE 35 mg/m2 X 4 DAYS Horse Antithymocyte Globulin 30 mg/kg X 5 DAYS
    Other Names:
    • Cytoxan
    • Fludara
    • horse Atgam
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.

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050439

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Mitchell S Cairo, MD Columbia University
  More Information

No publications provided

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT01050439     History of Changes
Other Study ID Numbers: AAAB3095, CHNY-02-516
Study First Received: June 3, 2008
Last Updated: July 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Allogeneic Stem Cell Transplant
Unrelated donor
Cord blood donor

Additional relevant MeSH terms:
Histiocytosis
Histiocytosis, Langerhans-Cell
Immunologic Deficiency Syndromes
Leukemia
Lymphoma
Pancytopenia
Hemoglobinuria, Paroxysmal
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Hematologic Diseases
Anemia, Hemolytic
Anemia
Myelodysplastic Syndromes
Bone Marrow Diseases
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 21, 2014