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Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies

This study has suspended participant recruitment.
(Study completed at site, no active participants. IDE open for future enrollment)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01419704
First Posted: August 18, 2011
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Duke University
Information provided by (Responsible Party):
University of Louisville
August 16, 2011
August 18, 2011
September 6, 2017
May 2011
May 2025   (Final data collection date for primary outcome measure)
Proportion of Hemoglobin A and S [ Time Frame: one month to three years ]
Red blood cell contents by hemoglobin electrophoresis
  • Proportion of Hemoglobin A and S [ Time Frame: one month to three years ]
    Red blood cell contents by hemoglobin electrophoresis
  • Donor chimerism [ Time Frame: one month to three years ]
    Percentage of donor cells as determined by molecular analysis
Complete list of historical versions of study NCT01419704 on ClinicalTrials.gov Archive Site
Enriched Hematopoetic Stem Cell Engraftment [ Time Frame: One month to three years ]
Occurrence of graft-versus-host disease (GVHD) [ Time Frame: One month to three years ]
Clinical manifestation of GVHD such as rash or intestinal involvement.
Not Provided
Not Provided
 
Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with hemoglobinopathies.
This proposal is a phase I/II feasibility study to demonstrate that mixed chimerism can be established with minimal risk in recipients with hemoglobinopathies treated with Campath-1H-based nonmyeloablative conditioning and graft engineering to reduce the risk of Graft Versus Host Disease (GVHD), but preserve engraftment of donor cells.
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Anemia, Sickle Cell
  • Complex and Transfusion-dependent Hemoglobinopathies
  • Thalassemia
  • Diamond-Blackfan Anemia
  • Bone Marrow Failure Syndromes
  • Alpha-Thalassemia
  • Beta-Thalassemia
Biological: Enriched Hematopoetic Stem Cell Infusion
Enriched Hematopoetic Stem Cell Infusion
Experimental: Hemoglobinopathies diagnosed patients
Recipients diagnosed with Hemoglobinopathies are treated with an enriched hematopoetic stem cell infusion from living donor bone marrow
Intervention: Biological: Enriched Hematopoetic Stem Cell Infusion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
30
May 2030
May 2025   (Final data collection date for primary outcome measure)
  1. Inclusion Criteria

    The following criteria are established to identify subjects with hemoglobinopathies, hematologic or bone marrow failure syndromes who have a high predicted morbidity and are at risk for early mortality:

    • Patients with alpha or beta thalassemia major.
    • Patients with Diamond-Blackfan anemia and other bone marrow failure syndromes, characterized by severe chronic anemia.
    • Patients with other complex and transfusion-dependent hemoglobinopathies, including sickle cell disease.
    • Patients with sickle disease who have one or more of the following:

      • Overt or silent stroke
      • Neurocognitive impairment
      • Pain crises 2 or more episodes per year for past year
      • One or more episodes of acute chest syndrome
      • Osteonecrosis involving 1 or more joints
      • Evidence of retinopathy
      • Priapism
      • Microalbuminuria or evidence of sickle cell nephropathy
      • Alloimmunization

    Subjects must also meet all of the following general inclusion criteria:

    • Subjects must have a related donor which can consist of Histocompatibility Leukocyte Antigen (HLA)-matched donor up to haploidentical match, mismatched for 1, 2 or 3 HLA-A, B or -DR loci.
    • Subjects must have adequate cardiopulmonary function as documented by echocardiogram or radionuclide scan. (Shortening fraction >26% or ejection fraction >40% or ≥ 80% of normal value for age).
    • Subjects must have adequate pulmonary function documented by Forced expiratory volume in 1 second (FEV1) of ≥ 50% of predicted for age and/or Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) ≥50% of predicted for age for patients > 10 years of age.
    • Subjects must have adequate hepatic function as demonstrated by a serum albumin ≥ 3.0 mg/dL, and serum glutamic pyruvic transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 5 times the upper limit of normal. Liver biopsy or a liver MRI is necessary if the patient has received chronic transfusions for over a year and/or has a ferritin level of ≥ 1600.
    • Subjects must have adequate renal function as demonstrated by a serum creatinine less than or equal to 2 mg/dL. If serum creatinine is ≥ 2 mg/dL, then a creatinine clearance test or nuclear medicine GFR should document GFR of ≥ 50 ml/min/1.73 m2.
    • Subjects or legal guardians must give written informed consent.
    • Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).
    • Less than or equal to 45 years of age.
  2. Exclusion Criteria

    • Patients with cirrhosis, extensive bridging hepatic fibrosis, or active hepatitis are excluded from enrollment.
    • Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, indicate that the patient could not tolerate reduced intensity transplantation.
    • Severe impairment of functional performance as evidenced by a Karnofsky score <70% (patients ≥16 years old) or Lansky (children <16 years old) score <70%
    • Renal insufficiency (GFR <50 ml/min/1.73 m2).
    • Subjects with a positive human immunodeficiency virus (HIV) antibody test result.
    • Subjects who are pregnant, as indicated by a positive serum human chorionic gonadotrophin (HCG) test.
    • Subjects whose only donor is pregnant at the time of intended transplant.
    • Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site.
    • Allogeneic hematopoietic stem cell transplant within the previous 1 year.
    • Subjects must not have had previous radiation therapy that would preclude total body irradiation (TBI) (as determined by a radiation therapist).
    • Jehovah's Witness unwilling to be transfused .
    • Uncontrolled hypersplenism.
    • Severe alloimmunization with inability to guarantee a supply of adequate packed red blood cell (PRBC) donors.
    • Subjects with thalassemia who are Lucarelli Class 3
    • Fanconi anemia.
    • Insufficient funds for the bone marrow processing costs
Sexes Eligible for Study: All
up to 45 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01419704
ICT-13881-012011
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
University of Louisville
University of Louisville
Duke University
Study Director: Suzanne T Ildstad, MD University of Louisville
University of Louisville
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP