CD34+Selection for Partially Matched Family or Matched Unrelated Adult Donor Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by New York Medical College
Sponsor:
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College
ClinicalTrials.gov Identifier:
NCT01049854
First received: May 5, 2008
Last updated: March 23, 2016
Last verified: March 2016
  Purpose
CD34+ stem cell selection in children, adolescents and young adults receiving partially matched family donor or matched unrelated adult donor allogeneic bone marrow or peripheral blood stem cell transplant will be safe and well tolerated and be associated with a low incidence of serious (Grade III/IV) acute and chronic graft versus host disease (GVHD).

Condition Intervention Phase
Leukemia
Lymphoma
Bone Marrow Failure
Immunodeficiencies
Histiocytosis
Sickle Cell Disease
Beta Thalassemia
Inborn Errors of Metabolism
Drug: Full Intensity with TBI
Drug: Full Intensity
Drug: Reduced Intensity
Drug: Reduced Intensity (Fanconi)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CD34+Stem Cell Selection for Patients Receiving Partially Matched Family or Matched Unrelated Adult Donor Allogeneic Stem Cell Transplantations for Malignant and Non-Malignant Disease

Resource links provided by NLM:


Further study details as provided by New York Medical College:

Primary Outcome Measures:
  • The safety CD34+ stem cell selection [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    serious adverse events will be monitored post transplant to determine if there is an increase vs. historical data related to the CD34+ selection


Secondary Outcome Measures:
  • Immune reconstitution (T, B, DC) following CD34+ selection [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    immune subsets will be drawn post transplant to determine the rate of reconstitution post CD34+ transplant to determine if this process increases or decreases the reconstitution time.


Estimated Enrollment: 35
Study Start Date: September 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thiotepa/Cyclophosphamide/ATG
Full intensity with TBI
Drug: Full Intensity with TBI
Patients will start their pre-conditioning regimen on Day -8. Fractionated TBI will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5, -4, Cyclophosphamide on Days -3, -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.
Other Names:
  • ThioTepa
  • Cytoxan
  • Atgam
Experimental: Busulfan/Melphalan/ATG
Full intensity without TBI
Drug: Full Intensity
Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with stem cell infusion on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.
Other Names:
  • Myleran
  • Alkeran
  • Atgam
Experimental: Busulfan/Fludarabine/Alemtuzumab
Reduced Intensity Chemotherapy
Drug: Reduced Intensity
Patients will start their GVHD prophylaxis with Tacrolimus on Day -9. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.
Other Names:
  • Fludara
  • Myleran
  • Campath
Experimental: Fludarabine/Cyclophosphamide/ATG
Reduced Intensity Chemotherapy for Fanconi Anemia
Drug: Reduced Intensity (Fanconi)
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and antithymocyte globulin (horse) on Days -5, -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.
Other Names:
  • Fludara
  • Cytoxan
  • Atgam

Detailed Description:

The selection of CD34+ cells is associated with the simultaneous depletion of T cells that are responsible for severe acute and chronic graft versus host disease (GVHD). Successful engraftment is reported in adult patients with malignant and non-malignant disease who received CD34+ selected stem cells from HLA-matched or mismatched mobilized peripheral blood (PBSC) or bone marrow.

Study Design:

Selected patients defined in the eligibility criteria will enrolled on this study. 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 and will have peripheral blood undergo CD34 selection.

  Eligibility

Ages Eligible for Study:   up to 70 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adequate renal function defined as:Serum creatinine <1.5 x normal, or Creatinine clearance or radioisotope GFR >60 ml/min/m2 or an equivalent GFR as determined by the institutional normal range.
  • Adequate liver function defined as:Total bilirubin <1.5 x normal, or SGOT (AST) or SGPT (ALT) <3.0 x normal
  • Adequate cardiac function defined as:Shortening fraction >27% by echocardiogram, or Ejection fraction of >47% by radionucleotide angiogram or echocardiogram.
  • Adequate pulmonary function defined as:Uncorrected DLCO >50% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air.

Eligibility for Reduced Intensity Regimen:

  • Adequate renal function defined as:Serum creatinine 2.0 x normal, or creatinine clearance or radioisotope GFR > 40 ml/min/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.

Exclusion Criteria:

  • Pregnancy/Breast Feeding: Females who are pregnant or breast-feeding are not eligible.
  • Infection: Patients with documented uncontrolled infection at the time of study entry are not eligible.
  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: NCT01049854

Contacts
Contact: Mitchell S Cairo, MD 914-594-2150 Mitchell_Cairo@nymc.edu
Contact: Lauren Harrison, RN 617-285-7844 lauren_harrison@nymc.edu

Locations
United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Lauren Harrison, RN    617-285-7844    lauren_harrison@nymc.edu   
Sponsors and Collaborators
New York Medical College
Investigators
Principal Investigator: Mitchell S Cairo, MD New York Medical College
  More Information

Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT01049854     History of Changes
Other Study ID Numbers: L 10,321  NYMC 525 
Study First Received: May 5, 2008
Last Updated: March 23, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by New York Medical College:
unrelated donor transplant
CD34 selection

Additional relevant MeSH terms:
Anemia, Sickle Cell
Immunologic Deficiency Syndromes
Thalassemia
Beta-Thalassemia
Pancytopenia
Histiocytosis
Metabolism, Inborn Errors
Immune System Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Lymphatic Diseases
Metabolic Diseases
Cyclophosphamide
Fludarabine phosphate
Busulfan
Thiotepa
Fludarabine
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 30, 2016