Status:
COMPLETED
Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
Lead Sponsor:
Talaris Therapeutics Inc.
Collaborating Sponsors:
Duke University
St. Christopher's Hospital for Children
Conditions:
Sickle Cell Disease
Eligibility:
All Genders
Phase:
PHASE1
PHASE2
Brief Summary
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with Hemoglobinopathies to halt disease progression.
Detailed Description
Hematopoietic stem cell transplantation (HSCT) is emerging as a therapeutic alternative for patients with sickle cell disease. Conventional HSCT therapy has been limited to extremely high-risk hemoglo...
Eligibility Criteria
Inclusion
- The following criteria are established to identify subjects with sickle cell disease (SCD) who have a high predicted morbidity and are at risk for early mortality. Subjects with S/S disease, S/C disease, Hemoglobin H disease, Alpha Thalassemia Major, Thalassemia Major (also known as Cooley's anemia) or S/B\* thalassemia and one or more of the following medical complications will be eligible:
- History of impaired neurological function and/or findings on Magnetic Resonance Image (MRI)/Magnetic Resonance Angiogram (MRA) that are associated with sickle cell disease
- More than 1 episode of acute chest syndrome with stage I or II pulmonary disease
- Osteonecrosis involving ≥ 2 joints
- Sickle cell nephropathy as evidenced by a glomerular filtration rate of 30% - 50% of the predicted normal
- Alloimmunization that is sufficient to interfere with the efficacy of chronic transfusion therapy
- Chronic or recurrent priapism
- Major visual impairment in one or both eyes with bilateral proliferative retinopathy
- Persistent disabling pain (≥ 2 episodes per year) despite trials of chronic transfusion and/or hydroxyurea at recommended doses for at least 6 months duration
- Additional General Criteria:
- Subjects must also meet all of the following general inclusion criteria:
- Subjects must have a related donor (identical or mismatched for 1, 2 or 3 HLA- A, HLA-B or HLA-DR loci).
- Subjects must have adequate cardiopulmonary function as documented by a left ventricular ejection fraction ≥ 50% (or within normal limits per Institutional criteria) or a left ventricular shortening fraction Within normal limits (WNL) per Institutional criteria, without inotropic support. If Ejection fraction is 40-50%, the patient may be considered for participation if cleared by a Cardiologist.
- Subjects must have adequate pulmonary function as documented by Diffusing capacity of the lung for carbon monoxide (DLCO) and Forced expiratory volume in 1 second (FEV1)
- 50% predicted for age and size. If DLCO and FEV1 are between 40-50%, patient may be considered for participation if cleared by a Pulmonologist.
- 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) ≤ 2.5 times the upper limit of normal.
- Subjects must have adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dL. If serum creatinine is ≥ 1.5 mg/dL, then a creatinine clearance test must be done and the result 50% of normal.
- Subjects or legal guardians must give written informed consent, and subjects must assent where age and intellectually appropriate.
- There are no age limits for this protocol.
Exclusion
- Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate transplantation.
- Severe impairment of functional performance as evidenced by a Karnofsky (patients ≥16 years old) or Lansky (children \<16 years old) score \<70%
- Stage III or IV sickle cell pulmonary disease
- Renal insufficiency (GFR \< 25% of predicted normal for age)
- 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 of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site
- Subjects must not have had previous radiation therapy that would preclude total body irradiation (as determined by a radiation oncologist).
Key Trial Info
Start Date :
January 1 2005
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 1 2013
Estimated Enrollment :
9 Patients enrolled
Trial Details
Trial ID
NCT00777231
Start Date
January 1 2005
End Date
August 1 2013
Last Update
October 14 2020
Active Locations (3)
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1
University of Louisville
Louisville, Kentucky, United States, 40202
2
Duke University Medical Center
Durham, North Carolina, United States, 27705
3
St. Christopher's Hospital for Children
Pittsburgh, Pennsylvania, United States, 19134