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Bone Marrow Failure SyndromesEarly Phase 1NCT02928991

Fludarabine Based RIC for Bone Marrow Failure Syndromes

A Early Phase 1 study testing MRD-BMT with Fludarabine-based RIC for Acquired AA, MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia and MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia in people with Bone Marrow Failure Syndromes, run by Children's Hospital of Philadelphia at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT). Read more about this study

Who is it for?
Ages Up to 22 years
Conditions the study is for
Bone Marrow Failure Syndromes
What is being tested?
MRD-BMT with Fludarabine-based RIC for Acquired AA, MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia and MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
Apr 2015to Dec 2028
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 22 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patient:
  • Ages 0-22 years at time of enrollment
  • Diseases:
  • Patients with severe or very severe acquired AA, defined by:
  • Bone marrow biopsy demonstrating cellularity of <25% (at least 2 weeks from last dose of G-CSF), in addition to 2 of the following: absolute neutrophil count (ANC) <500/µL, platelets < 20,000/µL and absolute reticulocytes <40,000/µL
  • Negative evaluation for inherited bone marrow failure conditions and negative evaluation for dysplasia or cytogenetic abnormalities associated with myelodysplastic syndromes
Show all 31Show fewer
  • Patients with concurrent paroxysmal nocturnal hemoglobinuria (PNH) clones are eligible, as long as they meet criteria for severe or very severe aplastic anemia as defined above
  • Patients with clinically diagnosed and/or genetically proven iBMF syndromes, resulting in chronic red blood cell or platelet-transfusion dependence and/or an absolute neutrophil count <500/µL. These disorders include, but are not limited to:
  • Fanconi Anemia
  • Dyskeratosis Congenita
  • Severe Congenital Neutropenia
  • Diamond-Blackfan Anemia
  • Congenital Dyserythropoietic/Sideroblastic Anemias
  • Congenital Amegakaryocytic Thrombocytopenia
  • Shwachman-Diamond Syndrome
  • Lansky or Karnofsky performance >60
  • HLA matched related donor available.
  • No active untreated infection
  • Females of childbearing potential must have negative pregnancy test.
  • Organ Function:
  • Serum creatinine <1.5xupper limit of normal for age Hepatic: Transaminases <5x normal
  • Cardiac shortening fraction >27%
  • Bilirubin <2.5x normal (unless elevation due to Gilberts disease).
  • Donor Selection Criteria:
  • Donor selection will comply with U.S. Food and Drug Administration's Code of Federal Regulations
  • Fully HLA-matched related donor.
  • Donor must be at least 6 months of age
  • Donor suitable for bone marrow collection and meets eligibility for donation, including fulfilling infectious disease criteria as per SOP, including HIV, Hepatitis B, Hepatitis C Polymerase chain reaction (PCR) negative.
  • If subject has confirmed iBMF syndrome, donor must be evaluated for this disorder and testing must be negative
  • Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
  • Donor evaluation and collection procedure as per CHOP Standard Operating Procedures (SOP)

Who cannot join

  • Uncontrolled bacterial, viral or fungal infections
  • HLA matched related donor unable to donate bone marrow.
  • No eligible fully HLA-matched related donor
  • Pregnant females
  • Patients with a clinical diagnosis of Myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts.
  • Patients with PNH without underlying bone marrow aplasia

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Fludarabine-Based Conditioning for Matched Related Donor Bone Marrow Transplantation in Patients With Bone Marrow Failure Syndromes

This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).

Read the detailed description

Acquired AA patients will receive the experimental regimen of fludarabine with dose-reduced cyclophosphamide, with results in this prospective single arm experimental group evaluated in the context of our institutional historical experience using HD Cy regimens as well as published outcomes using both fludarabine and high-dose cyclophosphamide-based regimens for MRD-BMT in aplastic anemia. iBMF syndrome patients will receive one of two fludarabine-containing regimens based on disease characteristics, and our outcomes will be compared to previously published data using a variety of regimens. Graft versus host disease (GvHD) prophylaxis will consist of cyclosporine/tacrolimus alone for patients with acquired AA or cyclosporine/tacrolimus plus mycophenolate for patients with iBMF syndromes. For both acquired AA and iBMF syndrome patients, donor chimerism will be assessed at scheduled intervals following BMT and will be used to define patients with full donor or mixed chimerism for comparisons of survival, graft failure, cytogenetic, GvHD, and immune reconstitution outcomes.

Being tested
MRD-BMT with Fludarabine-based RIC for Acquired AA, MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia, MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia
Keywords
Acquired aplastic anemia, Inherited bone marrow failure
Medical subject headings
Bone Marrow Failure Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MRD-BMT with Fludarabine-based RIC for Acquired AAOther

    Fludarabine: Dose: 30mg/m2/day (<10kg will receive 1mg/kg/day) Days: -7, -6, -5, -4, -3

    Cyclophosphamide: Dose: 60mg/kg/day Days: -5, -4

    Thymoglobulin: Dose: 3mg/kg/day Days: -4, -3, -2

    Bone marrow infusion: Day 0

  • MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasiaOther

    Fludarabine: Dose: 30mg/m2/day (<10kg will receive 1mg/kg/day) Days: -7, -6, -5, -4, -3

    Cyclophosphamide: Dose: 10 mg/kg/day Days: -6, -5, -4, -3

    Thymoglobulin: Dose: 3mg/kg/day Days: -4, -3, -2

    Bone marrow infusion: Day 0

  • MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasiaOther

    Fludarabine: Dose: 30mg/m2/day (<10kg will receive 1mg/kg/day) Days: -6, -5, -4, -3, -2

    Busulfan: Dose: every 6 hours for a total of 12 doses with dosing adjustments to achieve a steady state concentration of 900-1200ng/mL OR daily for a total of 3 doses targeting AUC 3600-6000 (micromole/liter)*minute Days: -7, -6, -5, -4

    Thymoglobulin: Dose: 3mg/kg/day Days: -10, -9, -8

    Bone marrow infusion: Day 0

Study groups in NCT02928991
Study groupRoleWhat they receive
Acquired Aplastic Anemia (AA)ExperimentalPatients with severe or very severe acquired aplastic anemia (AA). Patients will receive a matched related donor bone marrow transplant following reduced intensity conditioning (RIC) including thymoglobulin (ATG), fludarabine and dose-reduced cyclophosphamide.
Receives: Other: MRD-BMT with Fludarabine-based RIC for Acquired AA
Inherited Bone Marrow Failure Syndrome + Trilineage AplasiaExperimentalPatients with inherited bone marrow failure (iBMF) syndromes with trilineage aplasia includes those with diagnoses of Fanconi Anemia, Dyskeratosis Congenita, and related conditions. Patients will receive a matched related donor bone marrow transplant following conditioning with fludarabine, cyclophosphamide, thymoglobulin.
Receives: Other: MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia
Inherited Bone Marrow Failure Syndrome no Trilineage AplasiaExperimentalPatients with inherited bone marrow failure (iBMF) syndromes without trilineage aplasia includes those with diagnoses of Severe Congenital Neutropenia, Diamond-Blackfan Anemia, and related conditions. Patients will receive a matched related donor bone marrow transplant following conditioning with thymoglobulin, busulfan and fludarabine.
Receives: Other: MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of graft failure

    Combined rate of primary and secondary graft failure. Primary graft failure is defined as no evidence of neutrophil engraftment by day +28 after stem cell infusion. Secondary graft failure is defined as an ANC<100 for >7-10 days after initial engraftment occurs and is confirmed by hypocellular bone marrow biopsy and donor engraftment <20%.

    Measured: Up to 1 year post transplant

  2. Time to neutrophil engraftment

    The time from the day of transplant until neutrophil engraftment, which is defined as the first day of ANC >500/ul for the first of 3 consecutive days.

    Measured: Up to 1 year post transplant

  3. Transplant-related mortality

    Measured: Up to 100 days post transplant

Secondary outcomes (2)

  1. Rate of overall survival

    Measured: Up to 1 year post transplant

  2. Rate of disease free survival

    Measured: Up to 1 year post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2016 (estimated)
  2. Study startApr 2015
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02928991
Sponsor's protocol ID
14-011465
Other IDs
14BT057
Status last verified
May 2026
First submitted
7 Oct 2016
Last updated
28 May 2026
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing MRD-BMT with Fludarabine-based RIC for Acquired AA, MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia and MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia in people with Bone Marrow Failure Syndromes, run by Children's Hospital of Philadelphia at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of graft failure (time frame: Up to 1 year post transplant). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02928991.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026; AzTrials last refreshed its copy on 31 Oct 2026.

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