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Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells

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ClinicalTrials.gov Identifier: NCT01174108
Recruitment Status : Recruiting
First Posted : August 3, 2010
Last Update Posted : January 26, 2023
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:


  • Stem cell transplants from related donors (allogenic stem cell transplants) can be used to treat individuals with certain kinds of severe blood diseases or cancers, such as severe anemia. Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient. Because stem cell transplants can have serious complications, researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications.
  • By reducing the number of white blood cells included in the blood taken during the stem cell collection process, and replacing them with a smaller amount of white blood cells collected prior to stem cell donation, the stem cell transplant may be less likely to cause severe complications for the recipient. Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications.


- To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient.


  • Recipient: Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants.
  • Donor: Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood. OR unrelated donors found through the National Marrow Donor Program.


  • All participants will be screened with a physical examination and medical history.
  • Donors will undergo an initial apheresis procedure to donate white blood cells.
  • After the initial donation, donors will receive injections of filgrastim to release bone marrow cells into the blood.
  • After 5 days of filgrastim injections, donors will have apheresis again to donate stem cells that are present in the blood.
  • Recipients will provide an initial donation of white blood cells to be used for research purposes only.
  • From 7 days before the stem cell transplant, participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide, fludarabine, and anti-thymocyte globulin to suppress their immune system and prepare for the transplant.
  • After the initial chemotherapy, participants will receive the donated white blood cells and stem cells as a single infusion.
  • After the stem cell and white blood cell transplant, participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells. Participants will have three doses of methotrexate within the week after the transplant, but will continue to take cyclosporine for up to 4 months after the transplant.
  • Participants will remain in inpatient care for up to 1 month after the transplant, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.

Condition or disease Intervention/treatment Phase
Severe Aplastic Anemia MDS (Myelodysplastic Syndrome) Device: Miltenyi CD34 Reagent System Other: Donor derived G-CSF mobilized PBC Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-Cells
Actual Study Start Date : December 10, 2010
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2028

Arm Intervention/treatment
Experimental: 1
Target doses: CD34+ cells 8 x 106/kg; CD3+ cells 2 x 107/kg
Device: Miltenyi CD34 Reagent System
The CliniMACS CD34 Reagent System is a medical device that is used in vitro to select and enrich specific cell populations.

Other: Donor derived G-CSF mobilized PBC
Cell Therapy

No Intervention: 2

Primary Outcome Measures :
  1. Primary endpoint of this study is chronic GVHD by one year. [ Time Frame: 1 year ]
    chronic GVHD

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   4 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Recipient:

    • Patients diagnosed with one of the following hematologic diseases which are associated with reasonable longevity, shown to be curable by allogeneic BMT but where concern for a high procedural mortality with conventional BMT may delay or prevent such treatment:

      • 1) Paroxysmal nocturnal hemoglobinuria (PNH) associated with life-threatening thrombosis, and/or cytopenia, and/or transfusion dependence and/or recurrent and debilitating hemolytic crisis
      • 2) Severe aplastic anemia (SAA) or pure red cell aplasia (PRCA [acquired or congenital]) associated with transfusion dependence and/or neutropenia in patients who are not candidates for, or who have failed immunosuppressive therapy
      • 3) Refractory anemia (RA) or RARS MDS patients who have associated transfusion dependence and/or neutropenia.
    • Ages 4 to 80 (both inclusive), and weight >18kg
    • Availability of HLA identical or single HLA locus mismatched family donor or 10/10 matched unrelated donor at the allelic level (HLA alleles A, B, C, DR, and DQ).
    • 9/10 donors where all the HLA sequences have the same antigen/peptide binding domains in key exons to the patient. This can result in identical protein sequences between patient and donor. Allele mismatches in p and g groups can be considered acceptable due to the exact matching which exists in the binding domains.
    • Telomere Length Testing
    • Germline/Inherited gene panel in patients where a suspicion for a familial bone marrow failure syndrome (BMFS) exists, hTERC and hTERT, GATA2 mutation testing will be performed on protocol 04-H-0012 or performed elsewhere prior to enrolling on 04-H-0012.


- Recipient: any of the following

  • Major anticipated illness or organ failure incompatible with survival from PBSC transplant
  • Diffusion capacity of carbon monoxide (DLCO) <40% predicted (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed) using DL Adj and DL/VA/Adj.
  • Left ventricular ejection fraction <40% (evaluated by ECHO)
  • Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 ml/min by 24 hr urine collection
  • Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of normal
  • Pregnant or lactating
  • Fanconi s anemia
  • ECOG performance status of 3 or more (See Bone & Marrow Transplant Consortium Supportive Care Guidelines for HSCT Recipients)
  • Other malignant diseases liable to relapse or progress within 5 years, with the exception of a separate hematologic malignancy where allogeneic stem cell transplant has been shown to be potentially curative.
  • Presence of an active infection not adequately responding to appropriate therapy.
  • Inability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects age 8 -17 years with formal consent being obtained from parents or legal guardian.


-Related Donor:

  • Related donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood samples for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors, but study participation is not required for a donor to make a stem cell donation, so it is possible that not all related donors will enroll onto this study
  • Age greater than or equal to 4 and less than or equal to 80 years old


-Related Donor: None


- Donor eligibility will be completed per NMDP standards and in accordance with most recent and stringent FDA guidelines.

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 ClinicalTrials.gov identifier (NCT number): NCT01174108

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Contact: Melissa M Spencer, R.N. (301) 402-5609 melissa.spencer@nih.gov

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United States, Maryland
University of Maryland, Baltimore (UMB) Recruiting
Baltimore, Maryland, United States, 21201
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
United States, Minnesota
National Marrow Donor Program (NMDP) Recruiting
Minneapolis, Minnesota, United States, 55401
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Richard W Childs, M.D. National Heart, Lung, and Blood Institute (NHLBI)
Additional Information:
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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT01174108    
Other Study ID Numbers: 100154
First Posted: August 3, 2010    Key Record Dates
Last Update Posted: January 26, 2023
Last Verified: November 8, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: .Currently the protocol does not specify whether the IPD will be shared. The prospect of IPD sharing is currently under consideration by the PI.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Myelodysplastic Syndrome (MDS)
Severe Aplastic Anemia
Pure Red Cell Aplasia
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Miltenyi CD34 Reagent System
Additional relevant MeSH terms:
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Anemia, Aplastic
Myelodysplastic Syndromes
Bone Marrow Failure Disorders
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions