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Trial record 2 of 21 for:    Aplastic Anemia | Recruiting, Not yet recruiting, Available Studies | NIH, U.S. Fed

Haplo-Identical Transplantation for Severe Aplastic Anemia and Hypo-Plastic MDS Using Peripheral Blood Stem Cells and Post-Transplant Cyclophosphamide for GVHD Prophylaxis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03520647
Recruitment Status : Recruiting
First Posted : May 10, 2018
Last Update Posted : October 10, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:


Severe aplastic anemia (SAA) and myelodysplastic syndrome (MD) 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.


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


Recipients ages 4 55 with SAA or MD and their relative donors ages 4 75


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.

Condition or disease Intervention/treatment Phase
Severe Aplastic Anemia (SAA) Hypo-Plastic Myelodysplastic Syndrome (MDS) Procedure: haplo-identical transplantation Phase 2

Detailed Description:

Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are life-threatening bone marrow disorders. For SAA patients, long term survival can be achieved with immunosuppressive treatment. However, of those patients treated with immunosuppressive therapy, one quarter to one third will not respond, and about 50% of responders will relapse.

Although allogeneic stem cell transplantation (allo-SCT) offers the opportunity of cure, HLA-matched donors are available for only half the patients needing a transplant. Combined haplo-cord transplantation has recently been shown to be a viable transplant option for those patients lacking an HLA matched donor. In our ongoing protocol 08-H-0046, we have utilized this approach in 29 patients with SAA, and SAA evolving to MDS with 27/29 patients having sustained engraftment and achieving transfusion independence. However, engraftment patterns have varied substantially and in some patients, cord engraftment was profoundly delayed or never occurred.

Haploidentical peripheral blood stem cell transplantation (haplo-SCT) has the advantage over cord transplantation of immediate allograft availability, higher stem cell doses, and the feasibility of repeating cell collections if necessary for collecting CD34+ cells for stem cells boosts or lymphocytes to treat or prevent disease relapse or infection. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but most reports have focused on patients with hematological malignancies. At present, few data exist on the use of haploidentical transplantation using post-transplant cyclophosphamide for patients with aplastic anemia that have ATG-refractory disease and are heavily-transfused and HLA-alloimmunized. These patients are at an exceedingly high-risk for graft rejection compared to other patient populations.

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 that has proven to be refractory to conventional immunosuppressive therapy (IST) in patients who lack an HLA-matched donor (sibling/ or matched unrelated donor) and who do not have access to a good quality umbilical cord product that meets criteria for expansion (due to insufficient numbers of TNC and/or CD 34+ cells and/or inadequate HLA match) on NHLBI protocol number No. 17-H-0091.

The primary endpoint of the study is chronic GVHD-free survival (defined as the percentage of patients who are alive with no evidence of moderate or severe chronic GVHD at 1 year post-transplant). Secondary endpoints will include engraftment, 100 day and 200-day treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease. Health related quality of life will also be assessed as secondary outcome measure.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Haplo-identical Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using Peripheral Blood Stem Cells and Post-Transplant Cyclophosphomide for GVHD Prophylaxis
Actual Study Start Date : February 19, 2019
Estimated Primary Completion Date : June 1, 2025
Estimated Study Completion Date : June 1, 2028

Arm Intervention/treatment
Experimental: Transplant recipients
haplo-identical transplantation
Procedure: haplo-identical transplantation
Recipients will receive a non-myeloablative conditioning regimen of rabbit ATG 0.5 mg /kg (day-9) & 2 mg /kg (day -8, -7), Fludarabine 30 mg/m2 IV daily from day -6 to -2, Cyclophosphomide 14.5 mg/kg IV daily on day -6 and -5 and 200 cG of TBI on day -1; unmanipulated GCSF mobilized PBSC graft on day 0 and GVHD prophylaxis with Tacrolimus, MMF and post-transplant cyclophosphamide administered at a dose of 50mg/kg given daily on days +3 and +4 post-transplant.

Primary Outcome Measures :
  1. Evaluate 1 year chronic GVHD-free survival rate [ Time Frame: one-year ]
    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

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 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Diagnosed with severe aplastic anemia characterized by all the following:

    1. Bone marrow cellularity <30% (excluding lymphocytes)
    2. Transfusion dependence for platelets and/or RBCs
    3. Neutropenia ((absolute neutrophil count less than or equal to 1000 cells/ uL) OR for patients receiving granulocyte transfusions, absolute neutrophil count less than or equal to 1000 cells/ uL 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.
  • Intolerance of or failure to respond to standard immunosuppressive therapy.
  • Availability of at least one HLA- haploidentical (i.e. > 5/10 and less than or equal to 8/10 HLA match) related donor (HLA- A, B, C, DR, and DQ loci) who is available to donate stem cell graft (6-75 years old).
  • The patient does not have any HLA antibodies detectable against any of the mismatched HLA alleles expressed by the haplo-donor.
  • Ages 4-55 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.


  • Availability of an HLA identical or 9/10 HLA matched (HLA A, B, C, DR, and DQ loci) -relative to serve as a stem cell donor.
  • The patient is deemed to be a candidate for a 10/10 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).
  • The patient is eligible for transplantation using an ex vivo expanded cord blood unit on NHLBI protocol 17-H-0091
  • 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) or < 30% (evaluated by MUGA).
  • Transaminases > 5x upper limit of normal.
  • Serum bilirubin >4 mg/dl.
  • Creatinine clearance < 50 cc/min/BSAm2 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.


  • HLA mismatched family donor (greater than or equal to 5/10 and less than or equal to 8/10 HLA match (HLA-A, B, C, DR, and DQ loci)) who is available to donate cells.
  • Ages 4-75 inclusive. Note: a pediatric family member will only be considered as a donor if a suitable adult haplo-identical donor is not available.
  • Weight > 15 kg.
  • For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian who is not the recipient of the transplant and informed assent. The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
  • Genetic testing for genes associated with bone marrow failure syndromes (BMFS) performed at a CLIA- certified laboratory. If there is a suspicion of familial BMFS in the recipient, then the haplo donor must have undergone genetic testing for genes associated with BMFS - performed at a CLIA-certified laboratory, prior to enrolling in this protocol.


  • Pregnant or lactating.
  • A pediatric haplo-identical donor will be excluded if a suitable adult haplo-identical donor is available.
  • Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI, unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen).
  • HIV positive (Donors who are positive for HBV, HCV or HTLV I/II, T.cruzi [Chagas] may be used at the discretion of the investigator following counseling and approval from the recipient).
  • Sickling hemoglobinopathies including HbSS or HbSC. Donors with HbAS are acceptable.
  • Psychiatric illness that would limit the patient s ability to tolerate and/or comply with study requirements.
  • Screening test positive for Chagas disease (Trypanosoma cruzi /T. cruzi/trypanosomiasis) confirmed by the Center for Disease Control (CDC).

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 identifier (NCT number): NCT03520647

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Contact: Tatyana Worthy, R.N. (301) 594-8013

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United States, Maryland
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 TTY8664111010   
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) Identifier: NCT03520647     History of Changes
Other Study ID Numbers: 180090
First Posted: May 10, 2018    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 8, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Haploidentical CD34+cells
Additional relevant MeSH terms:
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Anemia, Aplastic
Myelodysplastic Syndromes
Hematologic Diseases
Bone Marrow Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists