- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00777231
Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
Study Overview
Status
Conditions
Intervention / Treatment
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 hemoglobinopathy patients. Those patients who may be difficult to identify before end-organ damage develops.
Also, conventional HSCT is only available to the minority of candidates who have Histocompatibility Leukocyte Antigen (HLA) identical siblings to donate bone marrow or mobilized peripheral blood stem cells.
This study proposes two important improvements over conventional HSCT:
- Donor peripheral blood or bone marrow will be processed via a new technology, which will deplete mature immune cells while enriching hematopoietic stem cells (HSC) and graft facilitating cells (FC).
- A reduced intensity recipient conditioning regimen will be used to promote mixed allogeneic chimerism, as opposed to full donor chimerism, following HSCT.
These two elements may significantly improve the benefit:risk ratio of HSCT for patients with hemoglobinopathies. Stem cell transplantation may become a more feasible option for patients that do not have HLA-identical siblings that can donate stem cells. Also, transplantation may be offered to patients earlier in the disease progression, before end-organ damage occurs.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Kentucky
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Louisville, Kentucky, United States, 40202
- University of Louisville
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North Carolina
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Durham, North Carolina, United States, 27705
- Duke University Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 19134
- St. Christopher's Hospital for Children
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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 Criteria:
- 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Sickle Cell Disease
Recipients treated with an enriched hematopoetic stem cell infusion
|
Enriched Hematopoetic Stem Cell Infusion
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EXPERIMENTAL: Non-Malignant Disorders
Recipients treated with an enriched hematopoetic stem cell infusion
|
Enriched Hematopoetic Stem Cell Infusion
|
EXPERIMENTAL: Aplastic Anemia
Recipients treated with an enriched hematopoetic stem cell infusion
|
Enriched Hematopoetic Stem Cell Infusion
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EXPERIMENTAL: Sickle Cell Disease : Extended Protocol
Recipients treated with an enriched hematopoetic stem cell infusion and Campath 1H conditioning
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Enriched Hematopoetic Stem Cell Infusion
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment
Time Frame: From one month to three years
|
Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.
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From one month to three years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Suzanne T Ildstad, M.D., Talaris Therapeutics Inc.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ICT-7621-042298
- 549.02 (OTHER: SCX UofL IRB)
- 430.98 (OTHER: SC StC IRB)
- 445.98 (OTHER: NM UofL IRB)
- 417.98 (OTHER: AA WIRB)
- Pro00009281 (OTHER: SC DU IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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