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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Duke University
Information provided by (Responsible Party):
University of Louisville
ClinicalTrials.gov Identifier:
NCT01419704
First received: August 16, 2011
Last updated: August 13, 2014
Last verified: August 2014

August 16, 2011
August 13, 2014
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 ] [ Designated as safety issue: No ]
Red blood cell contents by hemoglobin electrophoresis
Same as current
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 ] [ Designated as safety issue: No ]
Occurrence of graft-versus-host disease (GVHD) [ Time Frame: one month to three years ] [ Designated as safety issue: Yes ]
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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Anemia, Sickle Cell
  • Complex and Transfusion-dependent Hemoglobinopathies
  • Thalassemia
  • Alpha or Beta Thalassemia Major
  • Diamond-Blackfan Anemia
  • Bone Marrow Failure Syndromes Characterized by Severe Chronic Anemia
Device: Enriched Hematopoetic Stem Cell Transplantation
Bone marrow will be processed via a new technology which will enrich hematopoietic stem cells and graft facilitating cells. Monitoring for chimerism will be done at key time points.
Experimental: Enriched Hematopoetic Stem Cell Transplant
Intervention: Device: Enriched Hematopoetic Stem Cell Transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
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
Both
up to 45 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01419704
ICT-13881-012011
Yes
University of Louisville
University of Louisville
Duke University
Principal Investigator: Suhag Parikh, MD Duke University
Principal Investigator: Roger H Herzig, MD University of Louisville
University of Louisville
August 2014

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