Improving the Results of Bone Marrow Transplantation for Patients With Severe Congenital Anemias

NCT00061568 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 03017003-H-0170
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

People with severe congenital anemias, such as sickle cell anemia and beta-thalassemia, have been cured with bone marrow transplantation (BMT). The procedure, however, is limited to children younger than the age of 16 because the risks are lower for children than for adults. The purpose of this study is to explore the use of a BMT regimen that, instead of chemotherapy, uses a low dose of radiation, combined with two immunosuppressive drugs. This type BMT procedure is described as nonmyeloablative, meaning that it does not destroy the patient s bone marrow. It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons. To participate in this study, patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor. Beyond the standard BMT protocol, study participants will undergo additional procedures. The donor will receive G-CSF by injection for five days; then his or her stem cells will be collected and frozen one month prior to BMT. Approximately one month later, the patient will be given two immune-suppressing drugs, Campath 1-H and Sirolimus, as well as a single low dose of total body irradiation and then the cells from the donor will be infused. Prior to their participation in this study, patients will undergo the following evaluations: a physical exam, blood work, breathing tests, heart-function tests, chest and sinus x-rays, and bone-marrow sampling.

Conditions

Congenital Hemolytic Anemia; Sickle Cell Disease

Keywords

Stem Cell Transplant; Low Dose Radiation; Alemtuzumab (Campath); Sirolimus (Rapamune); Donor Apheresis; Sickle Cell Anemia (SCA); Beta-Thalassemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Experience Treatment Success Following Stem Cell Transplant

  Number of participants that experience treatment success at one year following stem cell transplant. Treatment success is defined as full donor type hemoglobin on hemoglobin electrophoresis for patients with sickle cell disease and transfusion-independence for patients with beta-thalassemia.

  Up to 1 year

Secondary Outcomes (7)

• Mean Myeloid Chimerism Level

  up to 2 years

• Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as Defined by CIMBTR Criteria for Organ Stages of Acute GVHD.

  Up to 1 year

• Number of Participants Who Developed Limited or Extensive Chronic GVHD

  Day 100 up to 3 Years

• Number of Participants With Regimen Failure

  Up to 1 year

• Number of Participants With Disease-free Survival

  Up to 2 year

Study Arms (2)

Participants with Severe Beta-globin Disorders in Allogeneic Peripheral Blood Stem Cell Transplants

EXPERIMENTAL

Nonmyeloablative transplant regiment, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells from human leukocyte antigen-matched siblings.

Procedure: Peripheral blood hematopoietic progenitor cell (PBPC) transplant; Drug: Alemtuzumab; Drug: Sirolimus

Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor

EXPERIMENTAL

Participants received Filgrastim to mobilize peripheral blood stem cells for apheresis collection. Collected stem cells of donor will then be infused to HLA matched sibling.

Procedure: Peripheral blood hematopoietic progenitor cell Apheresis

Interventions

Alemtuzumab DRUG

Alemtuzumab

Also known as: Campath

Participants with Severe Beta-globin Disorders in Allogeneic Peripheral Blood Stem Cell Transplants

Peripheral blood hematopoietic progenitor cell Apheresis PROCEDURE

Donor-Peripheral blood hematopoietic progenitor cell (PBPC) apheresis

Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor

Sirolimus DRUG

Sirolimus

Also known as: Rapamune

Participants with Severe Beta-globin Disorders in Allogeneic Peripheral Blood Stem Cell Transplants

Peripheral blood hematopoietic progenitor cell (PBPC) transplant PROCEDURE

Peripheral blood hematopoietic progenitor cell (PBPC) transplant

Participants with Severe Beta-globin Disorders in Allogeneic Peripheral Blood Stem Cell Transplants

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• RECIPIENTS:
• Must fulfill one disease category from below:
• DISEASE SPECIFIC:
• Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end organ damage (A, B, C, D or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F):
• A. Stroke defined as a clinically significant neurologic event that is accompanied by and infarct on cerebral MRI
• an abnormal trans-cranial Doppler examination ( greater than or equal to 200m/s);
• B. Sickle cell related renal insufficiency defined by a creatinine level greater than or equal to 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephritic syndrome OR creatinine clearance less than 60mL/min/1.73m(2) for patients less than or equal to 16 years of age or less than 50mL/min for patients greater than or equal to 16 years of age OR requiring peritoneal or hemodialysis
• Age is less than or equal to 5 years of age with the upper limit of normal serum creatinine 0.8mg/dl
• Age is greater than 5 years or less than or equal to 10 years of age with the upper limit of normal serum creatinine 1.0mg/dl
• Age is greater than 10 years and less than or equal to 15 years of age the the upper limit of normal serum creatinine 1.2mg/dl
• Age greater than 15 years of age with the upper limit of normal serum creatinine 1.3mg/dl
• C. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5m/s in patients greater than or equal to 18 years of age at least 3 weeks after a vaso-occlusive crisis, OR
• D. Recurrent tricorporal priapism defined as at least two episodes of an erection lasting greater than or equal to 4 hours involving the corpora cavernosa and corpus spongiosa, OR
• E. Sickle hepatopathy defined as EITHER ferritin greater than 100mcg/L OR direct bilirubin greater than 0.4 mg/dL at baseline in patients greater than or equal to 18 years of age; OR
• F. Any one of the below complications:

You may not qualify if:

• RECIPIENT:
• (Any of the following would exclude the subject from participating)
• ECOG performance status of 3 or more or Lansky performance status of less than 40.
• Diffusion capacity of carbon monoxide (DLCO) less than 35% predicted. (corrected for hemoglobin and alveolar volume)
• Baseline oxygen saturation or less than 85 % or PaOa2 less than 70
• Left ventricular ejection fraction: less than 35% estimated by ECHO.
• Transaminases greater than 5 times the upper limit of normal for age
• Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen
• Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
• Pregnant or lactating
• Major ABO mismatch
• DONOR:
• None

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (8)

• Wayne AS, Schoenike SE, Pegelow CH. Financial analysis of chronic transfusion for stroke prevention in sickle cell disease. Blood. 2000 Oct 1;96(7):2369-72.

  PMID: 11001885 BACKGROUND

• Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303.

  PMID: 7993409 BACKGROUND

• Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22. doi: 10.1056/NEJM199505183322001.

  PMID: 7715639 BACKGROUND

• Kern KC, Inam Z, Hsieh MM, Tisdale JF, Fitzhugh CD, Limerick EM, Gebremeskel ASK, White T, Jordan LC, Lynch JK. Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease. Neurology. 2026 Jun 9;106(11):e218050. doi: 10.1212/WNL.0000000000218050. Epub 2026 May 14.

  PMID: 42133908 DERIVED

• Inam Z, Jeffries N, Link M, Coles W, Pollack P, Luckett C, Phang O, Harvey E, Martin T, Farrey T, Tisdale JF, Hsieh MM. Two Nonmyeloablative HLA-Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Regimens in Patients with Severe Sickle Cell Disease. Transplant Cell Ther. 2025 May;31(5):305-318. doi: 10.1016/j.jtct.2025.02.021. Epub 2025 Feb 24.

  PMID: 40010689 DERIVED

• Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.

  PMID: 36240296 DERIVED

• Hsieh MM, Fitzhugh CD, Weitzel RP, Link ME, Coles WA, Zhao X, Rodgers GP, Powell JD, Tisdale JF. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA. 2014 Jul 2;312(1):48-56. doi: 10.1001/jama.2014.7192.

  PMID: 25058217 DERIVED

• Hsieh MM, Kang EM, Fitzhugh CD, Link MB, Bolan CD, Kurlander R, Childs RW, Rodgers GP, Powell JD, Tisdale JF. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009 Dec 10;361(24):2309-17. doi: 10.1056/NEJMoa0904971.

  PMID: 20007560 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Hemolytic, Congenital; Anemia, Sickle Cell; beta-Thalassemia

Interventions

Transplantation; Alemtuzumab; Sirolimus

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemoglobinopathies; Thalassemia

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: John Tisdale, M.D.
• Organization: National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH)

johntis@nhlbi.nih.gov

301.402.6497

Study Officials

• John F Tisdale, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 29, 2003
• First Posted: May 29, 2003
• Study Start: July 16, 2004
• Primary Completion: January 20, 2023
• Study Completion (Estimated): January 20, 2028
• Last Updated: September 9, 2026
• Results First Posted: February 29, 2024

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately
• Access Criteria: Protocol is available to be shared upon request to PI.

Locations

US (1)