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

October 18, 2011 updated by: Columbia University

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

Reduced intensity conditioning followed by allogeneic stem cell transplantation will result in mixed/complete donor chimerism and potentially alter the natural history and outcome of patients with non-malignant diseases.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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 (AlloSCT) in patients with non-malignant diseases.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • James Garvin, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fludarabine
Drug: Fludarabine
Fludarabine/Busulfan/Alemtuzumab
Experimental: Cyclohosphamide 200
Drug: Cyclophosphamide
Cyclophosphamide/Fludarabine/TMG
Experimental: Cyclophosphamide 40
Drug: Cyclophosphamide 40
Cyclophosphamide/Fludarabine/ATG/TBI
Other Names:
  • Cyclophosphamide
Experimental: Cyclophosphamide 30
Drug: Cyclophosphamide 30
Cyclophosphamide /Fludarabine/TMG
Other Names:
  • Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Day 30, Day 60, Day 100, 1 year, 2 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Investigators

  • Principal Investigator: James Garvin, MD. PhD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (Anticipated)

May 1, 2012

Study Completion (Anticipated)

May 1, 2013

Study Registration Dates

First Submitted

November 23, 2009

First Submitted That Met QC Criteria

November 23, 2009

First Posted (Estimate)

November 25, 2009

Study Record Updates

Last Update Posted (Estimate)

October 19, 2011

Last Update Submitted That Met QC Criteria

October 18, 2011

Last Verified

October 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAB0170
  • CHNY-01-509 (Other Identifier: CU)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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