Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00957931
Recruitment Status : Terminated
First Posted : August 13, 2009
Last Update Posted : December 21, 2012
University of Minnesota - Clinical and Translational Science Institute
University of Alabama at Birmingham
Information provided by (Responsible Party):
Stanford University

Brief Summary:

The main purpose of this project is to cure patients with high risk Sickle cell disease and other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow transplantation. The patients enrolled in this study will be those who lack matched sibling donors and therefore have no other option but to undergo bone marrow transplantation using matched but unrelated bone marrow or umbilical cord blood from the national marrow donor program registry. Since bone marrow transplantation for these disorders using matched unrelated donors has two major problems i.e. engraftment, or , the process of new marrow being accepted and allowed to grow in the the patient; and graft-versus-host disease, or the process where the new marrow "rejects" the host or the patient, this study has been devised with methods to overcome these two problems and thus make transplantation from unrelated donors both successful in terms of engraftment and safe in terms of side effects, both acute and long term.

In order to accomplish these two goals, two important things will be done. Firstly, patients will get three medicines which are considered reduced intensity because they are not known to cause the serious organ damage seen with conventional chemotherapy. These medicines, however, do cause intense immune suppression so these can cause increased infections. Secondly, in addition to transplantation of bone marrow from unrelated donors, patients will also transplanted with mesenchymal stromal cells derived from the bone marrow of their parents. Mesenchymal stromal cells are adult stem cells that are normally found in the bone marrow and are thought to create the right background for the blood cells to grow. They have been shown in many animal and human studies to improve engraftment. In addition, they have a special property by which they prevent and are now even considered to treat graft versus host disease. Therefore, by using a reduced intensity chemotherapy regimen before transplant and transplanting mesenchymal stromal cells, we hope to improve engraftment while at the same time decrease the potential for severe side effects associated with a conventional transplant which uses extremely high doses of chemotherapy.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Thalassemia Diamond-Blackfan Anemia Procedure: Bone marrow transplantation Biological: Mesenchymal Stromal Cells Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study MUD HCT:Pts High Risk Sickle Cell,Other Non-Malignant RBC Disorders- Reduced Intensity Preparative Regimen, HAPLO-Identical Mesenchymal Stromal Cells
Study Start Date : March 2009
Estimated Primary Completion Date : August 2013

Arm Intervention/treatment
Experimental: Mesenchymal stromal cells Procedure: Bone marrow transplantation
Bone marrow transplantation using matched unrelated donors, reduced intensity conditioning regimen, and co-transplanting mesenchymal stromal cells derived from parental bone marrow.

Biological: Mesenchymal Stromal Cells

Primary Outcome Measures :
  1. No.of patients with stable engraftment post HCT. Stable engraftment-ANC >500 for 3 consecutive days, platelet count >50,000 for one week without transfusion; subsequently stable engraftment will be measured by percentage of donor cells. [ Time Frame: 6 weeks, 6 months, 1 year ]

Secondary Outcome Measures :
  1. To estimate overall survival rate and disease free survival rate at 6 months, and 1 year [ Time Frame: 6 months, 1 year ]

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Ages Eligible for Study:   1 Year to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with SCD 1-25 years of age with an HLA-identical, but unrelated, donor or 1 HLA allele mismatched bone marrow or up to 2 HLA antigen mismatched umbilical cord blood (UCB) donor with one or more of the following:

    • Stroke, CNS hemorrhage or a neurologic event lasting longer than 24 hours.
    • Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions.
    • Recurrent vaso-occlusive pain, 3 or more episodes per year for 3 years or more years; or recurrent priapism.
    • Impaired neuropsychological function and/or abnormal cerebral MRI scan or abnormal TCD.
    • Stage I or II sickle lung disease.
    • Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate (GFR) 30-50% of the predicted normal value).
    • Bilateral proliferative retinopathy and major visual impairment in at least one eye.
    • Osteonecrosis of multiple joints with documented destructive changes.
    • Requirement for chronic transfusions but with RBC alloimmunization >2 antibodies during long term transfusion therapy.
    • Failure of hydroxyurea (HU) therapy.
  • Patients aged 0-21 years with transfusion dependent alpha- or beta-thalassemia who have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor.
  • Patients aged 0-21 years with Diamond-Blackfan anemia who have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor. Diamond- Blackfan anemia patients will only be eligible if they have failed steroid therapy.

Exclusion Criteria:

  • Patients with one or more of the following:

    • Karnofsky or Lansky performance score <70 (See Appendices I and II).
    • Stage III-IV lung disease (Appendix III).
    • GFR<30% predicted normal values.
    • Pregnant or lactating females.
    • Active serious infection whereby patient has been on intravenous antibiotics for one week prior to study entry.
    • Any patient with AIDS or HIV seropositivity.
    • Any patient with invasive aspergillus infection within one year of study entry.
    • Psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00957931

United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Stanford University
University of Minnesota - Clinical and Translational Science Institute
University of Alabama at Birmingham
Principal Investigator: Sandhya Kharbanda, M.D. Stanford University

Responsible Party: Stanford University Identifier: NCT00957931     History of Changes
Other Study ID Numbers: MSC01
First Posted: August 13, 2009    Key Record Dates
Last Update Posted: December 21, 2012
Last Verified: December 2012

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Diamond-Blackfan
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Red-Cell Aplasia, Pure
Bone Marrow Diseases