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

Thalassemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01419704
• Other study ID #: ICT-13881-012011
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: May 2011
• Est. completion date: May 2016

Study information

• Verified date: March 2023
• Source: Talaris Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This proposal is a phase I/II feasibility study to demonstrate that mixed chimerism can be established with minimal risk in recipients with hemoglobinopathies treated with Campath-1H-based nonmyeloablative conditioning and graft engineering to reduce the risk of Graft Versus Host Disease (GVHD), but preserve engraftment of donor cells.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 45 Years

Eligibility

1. Inclusion Criteria

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 also meet all of the following general inclusion criteria:

• 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.

• Subjects must have adequate cardiopulmonary function as documented by echocardiogram or radionuclide scan. (Shortening fraction >26% or ejection fraction >40% or = 80% of normal value for age).

• Subjects must have adequate pulmonary function documented by Forced expiratory volume in 1 second (FEV1) of = 50% of predicted for age and/or Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) =50% of predicted for age for patients > 10 years of age.

• 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) less than or equal to 5 times the upper limit of normal. Liver biopsy or a liver MRI is necessary if the patient has received chronic transfusions for over a year and/or has a ferritin level of = 1600.

• Subjects must have adequate renal function as demonstrated by a serum creatinine less than or equal to 2 mg/dL. If serum creatinine is = 2 mg/dL, then a creatinine clearance test or nuclear medicine GFR should document GFR of = 50 ml/min/1.73 m2.

• Subjects or legal guardians must give written informed consent.

• Female patients of childbearing potential cannot be pregnant or lactating/breast-feeding and must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (e.g., oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).

• Less than or equal to 45 years of age.

2. Exclusion Criteria

• 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.

• Insufficient funds for the bone marrow processing costs

Related Conditions & MeSH terms

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

Intervention

Biological:
• Enriched Hematopoetic Stem Cell Infusion
Enriched Hematopoetic Stem Cell Infusion

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Louisville	Louisville	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Talaris Therapeutics Inc.	Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Hemoglobin A and S	Red blood cell contents by hemoglobin electrophoresis	one month to three years
Secondary	Enriched Hematopoetic Stem Cell Engraftment		One month to three years