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

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ClinicalTrials.gov Identifier: NCT00957931
Recruitment Status : Completed
First Posted : August 13, 2009
Results First Posted : August 6, 2018
Last Update Posted : August 6, 2018
Sponsor:
Collaborators:
University of Minnesota
University of Alabama at Birmingham
Information provided by (Responsible Party):
Sandhya Kharbanda, Stanford University

Tracking Information
First Submitted Date  ICMJE August 12, 2009
First Posted Date  ICMJE August 13, 2009
Results First Submitted Date  ICMJE May 30, 2018
Results First Posted Date  ICMJE August 6, 2018
Last Update Posted Date August 6, 2018
Actual Study Start Date  ICMJE March 2009
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
Count of Participants With Stable Engraftment Post Hematopoietic Cell Transplantation (HCT) [ Time Frame: Up to 1 year ]
Stable engraftment was defined as absolute neutrophil count (ANC) >500 cells /µL for 3 consecutive days and platelet count >50,000 for one week without transfusion; subsequently stable engraftment was measured by percentage of donor cells.
Original Primary Outcome Measures  ICMJE
 (submitted: August 12, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2018)
  • Overall Survival 6 Months Following HCT [ Time Frame: 6 months ]
    Overall survival is reported at the count of participants alive 6 months following HCT.
  • Overall Survival 1 Year Following HCT [ Time Frame: 1 year ]
    Overall survival is reported at the count of participants alive 1 year following HCT.
  • Count of Participants With Disease-free Survival 6 Months Following HCT [ Time Frame: 6 months ]
    Disease-free survival is defined as alive without underlying disease.
  • Count of Participants With Disease-free Survival 1 Year Following HCT [ Time Frame: 1 year ]
    Disease-free survival is defined as alive without underlying disease.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2009)
To estimate overall survival rate and disease free survival rate at 6 months, and 1 year [ Time Frame: 6 months, 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
Official Title  ICMJE Pilot Study MUD HCT:Pts High Risk Sickle Cell,Other Non-Malignant RBC Disorders- Reduced Intensity Preparative Regimen, HAPLO-Identical Mesenchymal Stromal Cells
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sickle Cell Disease
  • Thalassemia
  • Diamond-Blackfan Anemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Mesenchymal stromal cells
Interventions:
  • Procedure: Bone marrow transplantation
  • Biological: Mesenchymal Stromal Cells
Publications * Kharbanda S, Smith AR, Hutchinson SK, McKenna DH, Ball JB, Lamb LS Jr, Agarwal R, Weinberg KI, Wagner JE Jr. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow Transplant. 2014 Apr;20(4):581-6. doi: 10.1016/j.bbmt.2013.12.564. Epub 2013 Dec 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2012)
6
Original Estimated Enrollment  ICMJE
 (submitted: August 12, 2009)
35
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with sickle cell disease (SCD) 1-25 years of age with an HLA-identical, but unrelated, donor or 1 human leukocyte antigen (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, central nervous system (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 transcranial Doppler (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 bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00957931
Other Study ID Numbers  ICMJE MSC01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sandhya Kharbanda, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE
  • University of Minnesota
  • University of Alabama at Birmingham
Investigators  ICMJE
Principal Investigator: Sandhya Kharbanda, M.D. Stanford University
PRS Account Stanford University
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP