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

NCT01419704 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: ICT-13881-012011
• Study Type: interventional
• Target: N/A
• 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.

Conditions

Anemia, Sickle Cell; Complex and Transfusion-dependent Hemoglobinopathies; Thalassemia; Diamond-Blackfan Anemia; Bone Marrow Failure Syndromes; Alpha-Thalassemia; Beta-Thalassemia

Keywords

other hemoglobinopathies; chimerism; sickle cell; thalassemia; Marrow/Enriched Hematopoetic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Proportion of Hemoglobin A and S

  Red blood cell contents by hemoglobin electrophoresis

  one month to three years

Secondary Outcomes (1)

• Enriched Hematopoetic Stem Cell Engraftment

  One month to three years

Study Arms (1)

Hemoglobinopathies diagnosed patients

EXPERIMENTAL

Recipients diagnosed with Hemoglobinopathies are treated with an enriched hematopoetic stem cell infusion from living donor bone marrow

Biological: Enriched Hematopoetic Stem Cell Infusion

Interventions

Enriched Hematopoetic Stem Cell Infusion BIOLOGICAL

Enriched Hematopoetic Stem Cell Infusion

Hemoglobinopathies diagnosed patients

Eligibility Criteria

• Age: Up to 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The following criteria are established to identify subjects with hemoglobinopathies, hematologic or bone marrow failure syndromes who have a high predicted morbidity and are at risk for early mortality:
• Patients with alpha or beta thalassemia major.
• Patients with Diamond-Blackfan anemia and other bone marrow failure syndromes, characterized by severe chronic anemia.
• Patients with other complex and transfusion-dependent hemoglobinopathies, including sickle cell disease.
• Patients with sickle disease who have one or more of the following:
• Overt or silent stroke
• Neurocognitive impairment
• Pain crises 2 or more episodes per year for past year
• One or more episodes of acute chest syndrome
• Osteonecrosis involving 1 or more joints
• Evidence of retinopathy
• Priapism
• Microalbuminuria or evidence of sickle cell nephropathy
• Alloimmunization
• Subjects must have a related donor which can consist of Histocompatibility Leukocyte Antigen (HLA)-matched donor up to haploidentical match, mismatched for 1, 2 or 3 HLA-A, B or -DR loci.

You may not qualify if:

• Patients with cirrhosis, extensive bridging hepatic fibrosis, or active hepatitis are excluded from enrollment.
• Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, indicate that the patient could not tolerate reduced intensity transplantation.
• Severe impairment of functional performance as evidenced by a Karnofsky score \<70% (patients ≥16 years old) or Lansky (children \<16 years old) score \<70%
• Renal insufficiency (GFR \<50 ml/min/1.73 m2).
• 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 whose only donor is pregnant at the time of intended transplant.
• Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site.
• Allogeneic hematopoietic stem cell transplant within the previous 1 year.
• Subjects must not have had previous radiation therapy that would preclude total body irradiation (TBI) (as determined by a radiation therapist).
• Jehovah's Witness unwilling to be transfused .
• Uncontrolled hypersplenism.
• Severe alloimmunization with inability to guarantee a supply of adequate packed red blood cell (PRBC) donors.
• Subjects with thalassemia who are Lucarelli Class 3
• Fanconi anemia.

Sponsors & Collaborators

• Talaris Therapeutics Inc.: lead
• Duke University: collaborator

Study Sites (3)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Anemia, Diamond-Blackfan; Bone Marrow Failure Disorders; alpha-Thalassemia; beta-Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Diseases

Study Officials

• Suzanne T Ildstad, MD

  Talaris Therapeutics Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 16, 2011
• First Posted: August 18, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 3, 2023

Record last verified: 2023-03

Locations

US (3)