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

NCT01174108 | Recruiting Phase 2 FDA Device

• 2 other identifiers: 10015410-H-0154
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

Background:

• 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. Objectives: \- To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient. Eligibility:
• 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. Design:
• All participants will be screened with a physical examination and medical history.
• DONORS:
• 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:
• 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.

Conditions

MDS (Myelodysplastic Syndrome); Severe Aplastic Anemia

Keywords

Myelodysplastic Syndrome (MDS); Severe Aplastic Anemia; Pure Red Cell Aplasia; Paroxysmal Nocturnal Hemoglobinuria (PNH); Miltenyi CD34 Reagent System

Outcome Measures

Primary Outcomes (1)

• Primary endpoint of this study is chronic GVHD by one year.

  chronic GVHD

  1 year

Study Arms (2)

1

EXPERIMENTAL

Target doses: CD34+ cells 8 x 106/kg; CD3+ cells 2 x 107/kg

Device: Miltenyi CD34 Reagent System; Other: Donor derived G-CSF mobilized PBC

2

NO INTERVENTION

Donor

Interventions

Miltenyi CD34 Reagent System DEVICE

The CliniMACS CD34 Reagent System is a medical device that is used in vitro to select and enrich specific cell populations.

1

Donor derived G-CSF mobilized PBC OTHER

Cell Therapy

1

Eligibility Criteria

• Age: 4 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• \) Paroxysmal nocturnal hemoglobinuria (PNH) associated with life-threatening thrombosis, and/or cytopenia, and/or transfusion dependence and/or recurrent and debilitating hemolytic crisis
• \) Severe aplastic anemia (SAA) or pure red cell aplasia (PRCA \[acquired or congenital\]) with bone marrow cellularity \<30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count \<=1000 cells/uL or for patients receiving granulocyte transfusions, absolute neutrophil count \<=1000 cells/ uL before beginning granulocyte transfusions). in newly diagnosed patients and/or in patients who have failed immunosuppressive therapy.
• \) Refractory anemia (RA) or RARS MDS patients who have associated transfusion dependence and/or neutropenia.
• Ages 4 to 80 (both inclusive), and weight \>15 kg
• 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).
• /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) exist, hTERC and hTERT, GATA2 mutation testing will be performed on protocol 04-H-0012 or performed elsewhere prior to enrolling on 04-H-0012.

You may not qualify if:

• \- 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 (test to be performed at a CLIA-certified laboratory)
• ECOG performance status of 3 or more (See NIH Bone \& Marrow Transplant Consortium Supportive Care Guidelines for HSCT Recipients or Institutional Guidelines for bone and marrow transplants)
• 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

Sponsors & Collaborators

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

Study Sites (2)

University of Maryland, Baltimore (UMB)

Baltimore, Maryland, 21201, United States

COMPLETED

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Anemia, Refractory, with Excess of Blasts; Myelodysplastic Syndromes; Red-Cell Aplasia, Pure; Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Anemia, Refractory; Anemia, Hemolytic

Study Officials

• Richard W Childs, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa M Spencer, R.N.

CONTACT

(301) 402-5609; melissa.spencer@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2010
• First Posted: August 3, 2010
• Study Start: December 10, 2010
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 8, 2026

Record last verified: 2025-12-23

Locations

US (2)