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

Completed · Phase 1/Phase 2

Conditions studied: Sickle Cell Disease

In brief

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

Key facts

Study ID

NCT00777231

Run by

Talaris Therapeutics Inc.

People needed

9

Starts

2005-01-01

Expected to finish

2013-08-01

Last updated by the study team

2020-10-14

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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).

Where it is running

• University of Louisville — Louisville, Kentucky, United States
• Duke University Medical Center — Durham, North Carolina, United States
• St. Christopher's Hospital for Children — Pittsburgh, Pennsylvania, United States

Full record on ClinicalTrials.gov

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