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Clinical Trial VICCNCBMT12108


A Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients with Sickle Cell Disease and Other Hemoglobinopathies

Principal Investigator(s)

Adetola Kassim


  • Protocol No. VICCNCBMT12108
  • Open Date: 05/08/2013
  • Staging: N/A
  • Age Group: Both Child and Adult
  • Scope: Local
  • Objective: Obtain estimates of transplant-related mortality (TRM) and progression-free survival in patients with severe hemoglobinopathies receiving non-myeloablative conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives (mini-haploBMT) as well as HLAmatched donors.
  • Disease Sites: Sickle Cell
  • Therapies: Therapy (NOS)
  • Drugs: Cyclophosphamide (CTX); Filgrastim (GCSF); Fludarabine (Fludara); Mesna; Sirolimus; Thiotepa; Thymoglobulin
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01850108
  • Secondary Protocol No: Not Specified


None Provided.


Ages Eligible for Study:2 Years to 70 Years
Genders Eligible for Study:All
Accepts Healthy Volunteers:Accepts Healthy Volunteers


Inclusion Criteria:
Patients who are ineligible for BMT from an HLA-matched sibling donor can proceed to a haplo-BMT. Patients with an HLA-matched related donor will proceed to a matched BMT.
• Age 2-70 years
• Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
• Patients and donors must be able to sign consent forms. First degree relative should be willing to donate
• Patients must be geographically accessible and willing to participate in all stages of treatment.
• Eligible diagnoses: Patients with sickle cell anemia such as sickle cell anemia (Hb SS), Hb Sβ° thalassemia, Hb Sβ+ thalassemia, Hb SC disease, Hb SE disease, Hb SD disease, Hemoglobin SO- Arab disease HbS with hereditary persistence of fetal hemoglobin. Other significant hemoglobinopathies that also fulfill criterion from below.
Plus one of the following:
1. Stroke or central nervous system event lasting more than 24 hours.
2. MRI changes indicative of brain parenchyma damage.
3. MRA evidence of cerebrovascular disease.
4. Acute chest syndrome requiring exchange transfusion or hospitalization.
5. Recurrent vaso-occlusive pain episodes and hospitalization crisis (more than 2/year for the last 2 years).
6. Stage I or II sickle lung disease.
7. Transfusion dependent thalassemia
Exclusion Criteria:
Poor performance status (ECOG>1).
• Poor cardiac function: left ventricular ejection fraction<35%.
• Poor pulmonary function: FEV1 and FVC<40% predicted.
• Pulmonary hypertension moderate to severe by echocardiographic standards.
• Poor liver function: direct bilirubin >3.1 mg/dl
• HIV-positive
• Minor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available.
• Prior transfusions from donor or recipient if caused alloimmunization vs. donor cells.
• Women of childbearing potential who currently are pregnant (Beta-HCG+) or who are not practicing adequate contraception.
• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up.
Criteria for donor eligibility
• Weight ≥ 20kg and age ≥ 18 years
• Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) and will be screened per the American Association of Blood Banks (AABB). (AABB guidelines and the recipients will be informed of any deviations.)
• When more than one donor is available, the donor with the lowest number of HLA allele mismatches will be chosen, unless there is HLA cross-match incompatibility or a medical reason to select otherwise, in which case donor selection is the responsibility of the PI, in consultation with the immunogenetics laboratory. In cases where there is more than one donor with the least degree of mismatch,donors will be selected based on the most favorable combination of (i) HLA compatibility in cross-match testing and (ii) ABO compatibility:
• HLA crossmatching (in order of priority)
1. Mutually compatible (no cross-matching antibodies)
2. Recipient non-cross-reactive with donor, donor cross-reactive with recipient
3. Mutually cross-reactive
• ABO compatibility (in order of priority)
• Compatible
• Major incompatibility
• Minor incompatibility
• Major and minor incompatibility
• Donors will be selected to minimize HLA mismatch in the host-versus-graft direction.
• Donor must have a hemoglobin S =/< ~50%.