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
  Purpose

The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with hemoglobinopathies.


Condition Intervention Phase
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
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies

Resource links provided by NLM:


Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Enriched Hematopoetic Stem Cell Engraftment [ Time Frame: One month to three years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2011
Estimated Study Completion Date: May 2030
Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enriched Hematopoetic Stem Cell Transplant 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  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
  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: NCT01419704

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
University of Louisville
Duke University
Investigators
Principal Investigator: Suhag Parikh, MD Duke University
Principal Investigator: Roger H Herzig, MD University of Louisville
  More Information

No publications provided

Responsible Party: University of Louisville
ClinicalTrials.gov Identifier: NCT01419704     History of Changes
Other Study ID Numbers: ICT-13881-012011
Study First Received: August 16, 2011
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Louisville:
other hemoglobinopathies
chimerism
sickle cell
thalassemia
Marrow/Enriched Hematopoetic Stem Cell Transplant

Additional relevant MeSH terms:
Anemia
Anemia, Diamond-Blackfan
Anemia, Sickle Cell
Beta-Thalassemia
Hemoglobinopathies
Hemoglobinuria, Paroxysmal
Pancytopenia
Thalassemia
Anemia, Aplastic
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Anemia, Hypoplastic, Congenital
Bone Marrow Diseases
Genetic Diseases, Inborn
Hematologic Diseases
Myelodysplastic Syndromes
Red-Cell Aplasia, Pure

ClinicalTrials.gov processed this record on October 22, 2014