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

NCT00777231 | Completed Phase 1 DMC FDA Drug

• 6 other identifiers: ICT-7621-042298549.02430.98445.98417.98Pro00009281
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell; Stem Cell; Tolerance; Bone Marrow Transplant; Total Body Irradiation (TBI); Apheresis; Aplastic Anemia; Hemoglobinopathies; Non Malignant

Outcome Measures

Primary Outcomes (1)

• Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment

  Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.

  From one month to three years

Study Arms (4)

Sickle Cell Disease

EXPERIMENTAL

Recipients treated with an enriched hematopoetic stem cell infusion

Biological: Enriched Hematopoetic Stem Cell Infusion

Non-Malignant Disorders

EXPERIMENTAL

Recipients treated with an enriched hematopoetic stem cell infusion

Biological: Enriched Hematopoetic Stem Cell Infusion

Aplastic Anemia

EXPERIMENTAL

Recipients treated with an enriched hematopoetic stem cell infusion

Biological: Enriched Hematopoetic Stem Cell Infusion

Sickle Cell Disease : Extended Protocol

EXPERIMENTAL

Recipients treated with an enriched hematopoetic stem cell infusion and Campath 1H conditioning

Biological: Enriched Hematopoetic Stem Cell Infusion

Interventions

Enriched Hematopoetic Stem Cell Infusion BIOLOGICAL

Enriched Hematopoetic Stem Cell Infusion

Aplastic Anemia; Non-Malignant Disorders; Sickle Cell Disease; Sickle Cell Disease : Extended Protocol

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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 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)
• % 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.

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).

Sponsors & Collaborators

• Talaris Therapeutics Inc.: lead
• Duke University: collaborator
• St. Christopher's Hospital for Children: collaborator
• The Western Pennsylvania Hospital: collaborator
• University of Florida: collaborator
• Medical College of Pennsylvania Hospital: collaborator
• Hahnemann University Hospital: collaborator

Study Sites (3)

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

St. Christopher's Hospital for Children

Pittsburgh, Pennsylvania, 19134, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Anemia, Aplastic; Hemoglobinopathies

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Suzanne T Ildstad, M.D.

  Talaris Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: No control group used, single group for each of four different disease groups

Study Record Dates

• First Submitted: October 20, 2008
• First Posted: October 22, 2008
• Study Start: January 1, 2005
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2013
• Last Updated: October 14, 2020

Record last verified: 2020-10

Locations

US (3)