Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis

NCT03520647 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 18009018-H-0090
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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)

Keywords

Haploidentical CD34+cells; Non-Myeloablative

Outcome Measures

Primary Outcomes (1)

• Evaluate 1 year chronic GVHD-free survival rate

  evaluate 1 year chronic GVHD-free survival rate (defined by the percentage of patients who are alive with no evidence of moderate or severe chronic GVHD at 1 year) of using G-CSF mobilized peripheral stem cells and post haplo-identical transplantation cyclophosphamide in subjects with severe aplastic anemia or refractory anemia (RA) or SAA subjects

  one-year

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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

Drug: Cyclophosphamide; Other: Peripheral Blood Stem Cells

Interventions

Cyclophosphamide DRUG

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.

Treatment Arm

Peripheral Blood Stem Cells OTHER

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.

Treatment Arm

Eligibility Criteria

• Age: 4 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

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; Hemoglobinuria, Paroxysmal

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Richard W Childs, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer A Farren

CONTACT

(301) 594-8013; jennifer.farren@nih.gov

Richard W Childs, M.D.

CONTACT

(301) 768-9433; childsr@nhlbi.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: May 9, 2018
• First Posted: May 11, 2018
• Study Start: February 19, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-03-13

Locations

US (1)