Recruiting
Phase 2

Haplo-identical Transplantation

Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Code:

NCT03520647

Conditions

Severe Aplastic Anemia (SAA)

Hypo-Plastic Myelodysplastic Syndrome (MDS)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Eligibility Criteria

Sex: All

Age: 4 - 70+

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide

Peripheral Blood Stem Cells

Study Details

Brief summary:

Background:

Severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria

(PNH) cause serious blood problems. Stem cell transplants using bone marrow or blood plus chemotherapy can help. Researchers want to see if using peripheral blood stem cells (PBSCs) rather than bone marrow cells works too. PBSCs are easier to collect and have more cells that help transplants.

Objectives:

To see how safely and effectively SAA, MDS and PNH are treated using peripheral blood hematopoietic stem cells from a family member plus chemotherapy.

Eligibility:

Recipients ages 4-60 with SAA, MDS or PNH and their relative donors ages 4-75

Design:

Recipients will have:

  • Blood, urine, heart, and lung tests
  • Scans
  • Bone marrow sample

Recipients will need a caregiver for several months. They may make fertility plans and a power of attorney.

Donors will have blood and tissue tests, then injections to boost stem cells for 5-7 days.

Donors will have blood collected from a tube in an arm or leg vein. A machine will separate stem cells and maybe white blood cells. The rest of the blood will be returned into the other arm or leg.

In the hospital for about 1 month, recipients will have:

  • Central line inserted in the neck or chest
  • Medicines for side effects
  • Chemotherapy over 8 days and radiation 1 time
  • Stem cell transplant over 4 hours

Up to 6 months after transplant, recipients will stay near NIH for weekly physical exams and blood tests.

At day 180, recipients will go home. They will have tests at their doctor s office and NIH several times over 5 years.

Conditions

Severe Aplastic Anemia (SAA)

Hypo-Plastic Myelodysplastic Syndrome (MDS)

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study ID

NCT03520647

Start date

Feb 19, 2019

Status verified date

Jun 30, 2026

Completion date

Jun 1, 2028

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 4 - 70+

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA - RECIPIENT:
  • Diagnosed with severe aplastic anemia with bone marrow cellularity <30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count less than or equal to 1000 cells/ microL or for patients receiving granulocyte transfusions, absolute neutrophil count less than or equal to 1000 cells/microL before beginning granulocyte transfusions).

OR

--History of severe aplastic anemia transformed to MDS. that meet the following criteria: a) International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, b) <5% myeloblasts and <30% of cellularity in the bone marrow on screening morphologic analysis.

OR

  • PNH that is either refractory to treatment with eculizumab/ravulizumab or occurs in patients who don t have access to treatment with eculizumab associated with either a) life- threatening thrombosis and/or b) cytopenia associated with transfusion dependence and/or c) recurrent and debilitating hemolytic crisis.

  • Subjects with severe aplastic anemia, hypoplastic MDS or PNH with associated bone marrow failure syndromes who have intolerance of or failure to respond to immunosuppressive therapy. This also includes patients who have failed immunosuppressive therapy with ATG and cyclosporine or therapy with cyclosporine combined with eltrombopag in those who are intolerant of or do not have access to treatment with ATG.
  • Availability of at least one HLA- haploidentical related donor (i.e. >= 5/10 HLA match: HLA-A, B, C, DR, and DQ loci) to serve as a stem cell donor for the allogeneic transplant.
  • Availability of a backup stem cell source in the event of graft rejection:
  • at least one additional haploidentical related alternative donor (i.e. HLA- haploidentical related donor (i.e. >= 5/10 HLA match: HLA-A, B, C, DR, and DQ loci) or >= 9/10 HLA matched unrelated donor who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the haplo-transplant has been rejected.
  • umbilical cord blood unit/s that can be used for a salvage cord blood transplant in the event that the haplo-transplant has been rejected

  • The patient does not have any HLA antibodies detectable against any of the mismatched HLA alleles expressed by the haplo-donor.
  • Ages 4-60 years inclusive.
  • Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.

EXCLUSION CRITERIA - RECIPIENT (ANY OF THE FOLLOWING):

  • Availability of an HLA identical (12/12) matched related or unrelated donor who is available within optimal timeline and suitable considering graft source and established donor selection factors (e.g. age, sex, viral exposure, ABO compatibility, pregnancy status, etc) per PI discretion.
  • The patient is deemed to be a candidate for a 12/12 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).
  • ECOG performance status of 2 or more.
  • Major anticipated illness or organ failure incompatible with survival from transplant.
  • Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy, if of childbearing potential for one year.
  • HIV positive.
  • Diagnosis of Fanconi s anemia (by chromosome breakage study).
  • Diffusion capacity of carbon monoxide (DLCO) <40% using DLCO corrected for Hgb or lung volumes (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).
  • Left ventricular ejection fraction <40% (evaluated by ECHO)
  • Transaminases > 5x upper limit of normal.
  • Direct bilirubin >3 mg/dl.
  • Creatinine clearance < 50 cc/min/BSAm\^2 by 24-hour urine collection adjusted by body surface area.
  • Serum creatinine > 2.5 mg/dl
  • Presence of an active infection not adequately responding to appropriate therapy.
  • History of a malignant disease liable to relapse or progress within 5 years.

INCLUSION CRITERIA - DONOR:

Donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.

EXCLUSION CRITERIA - RELATED DONOR:

None

Study Design

Enrollment

56 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment Arm

G-CSF mobilized peripheral stem cells and post haplo-identical transplantation cyclophosphamide

Interventions

Cyclophosphamide

This research protocol is therefore designed to evaluate the safety and effectiveness of using an unmanipulated G-CSF mobilized peripheral stem cell allograft from a haploidentical donor and post-transplant cyclophosphamide for patients with SAA, or SAA evolving to MDS, or PNH that has proven to be refractory to conventional immunosuppressive therapy (IST) in patients who lack an HLA-matched donor (sibling/ or matched unrelated donor.

Peripheral Blood Stem Cells

This research protocol is therefore designed to evaluate the safety and effectiveness of using an unmanipulated G-CSF mobilized peripheral stem cell allograft from a haploidentical donor and post-transplant cyclophosphamide for patients with SAA, or SAA evolving to MDS, or PNH that has proven to be refractory to conventional immunosuppressive therapy (IST) in patients who lack an HLA-matched donor (sibling/ or matched unrelated donor.

Primary outcome measure

  • Evaluate 1 year chronic GVHD-free survival rate [ Time Frame: one-year ]

Central Contacts and Locations

Central contacts

Jennifer A Farren

(301) 318-2095jennifer.farren@nih.gov

Richard W Childs, M.D.

(301) 768-9433childsr@nhlbi.nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222prpl@cc.nih.gov

More Information

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Last update posted

Sep 8, 2026

Last verified

Jun 30, 2026

Keywords

  • Haploidentical CD34+cells
  • Non-Myeloablative

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Heart, Lung, and Blood Institute (NHLBI) on 2026-09-08.