NCT02928991

Brief 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).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for early_phase_1

Timeline
19mo left

Started Apr 2015

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress88%
Apr 2015Dec 2027

Study Start

First participant enrolled

April 1, 2015

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

October 7, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 10, 2016

Completed
10.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

May 20, 2025

Status Verified

May 1, 2025

Enrollment Period

11.7 years

First QC Date

October 7, 2016

Last Update Submit

May 15, 2025

Conditions

Bone Marrow Failure Syndromes

Keywords

Acquired aplastic anemiaInherited bone marrow failure

Outcome Measures

Primary Outcomes (3)

  • 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%.

    Up to 1 year post transplant

  • 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.

    Up to 1 year post transplant

  • Transplant-related mortality

    Up to 100 days post transplant

Secondary Outcomes (2)

  • Rate of overall survival

    Up to 1 year post transplant

  • Rate of disease free survival

    Up to 1 year post transplant

Study Arms (3)

Acquired Aplastic Anemia (AA)

EXPERIMENTAL

Patients 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.

Other: MRD-BMT with Fludarabine-based RIC for Acquired AA

Inherited Bone Marrow Failure Syndrome + Trilineage Aplasia

EXPERIMENTAL

Patients 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.

Other: MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia

Inherited Bone Marrow Failure Syndrome no Trilineage Aplasia

EXPERIMENTAL

Patients 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.

Other: MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia

Interventions

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

Acquired Aplastic Anemia (AA)
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

Inherited Bone Marrow Failure Syndrome + Trilineage Aplasia
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

Inherited Bone Marrow Failure Syndrome no Trilineage Aplasia

Eligibility Criteria

AgeUp to 22 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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
  • 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
  • +16 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Bone Marrow Failure Disorders

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • Timothy Olson, MD, PhD

    Children's Hospital of Philadelphia

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Atkinson

CONTACT

215-590-2820cttsbmtintake@chop.edu

Patricia Hankins, BSN, RN, CCRC

CONTACT

215-590-5168hankinsp@chop.edu

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

October 7, 2016

First Posted

October 10, 2016

Study Start

April 1, 2015

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2027

Last Updated

May 20, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will not share

Locations

US(1)