NCT02162420

Brief Summary

Fludarabine-based preparative regimen followed by an allogeneic hematopoietic stem cell transplant using related or unrelated donor in persons 0-70 years of age diagnosed with dyskeratosis congenita or severe aplastic anemia who have bone marrow failure characterized by a requirement for red blood cell and platelet transfusions. Three different preparative regimens are included based on disease and donor type.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
61

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 10, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 12, 2014

Completed
7 months until next milestone

Study Start

First participant enrolled

January 10, 2015

Completed
9.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 8, 2024

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 11, 2025

Completed
2 months until next milestone

Results Posted

Study results publicly available

May 8, 2025

Completed
Last Updated

May 8, 2025

Status Verified

May 1, 2025

Enrollment Period

9.6 years

First QC Date

June 10, 2014

Results QC Date

April 7, 2025

Last Update Submit

May 7, 2025

Conditions

Dyskeratosis CongenitaAplastic Anemia

Keywords

severe aplastic anemiaHematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (2)

  • Incidence of Neutrophil Engraftment

    Incidence of neutrophil engraftment by day 42.

    Day 42

  • Incidence of Platelet Engraftment

    Incidence of platelet engraftment at 1 year

    1 year

Secondary Outcomes (5)

  • Incidence of Regimen Related Mortality

    Day 100

  • Incidence of Acute Graft-versus-host Disease

    Day 100

  • Incidence of Chronic Graft-versus-host Disease

    6 Months

  • Incidence of Chronic Graft-versus-host Disease

    1 Year

  • Incidence of Secondary Malignancies

    1 Year

Study Arms (5)

Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)

EXPERIMENTAL

Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.

Drug: AlemtuzumabDrug: FludarabineDrug: CyclophosphamideBiological: Stem Cell Transplant

Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)

EXPERIMENTAL

Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.

Drug: AlemtuzumabDrug: FludarabineDrug: CyclophosphamideRadiation: Total Body IrradiationBiological: Stem Cell TransplantDrug: Anti-thymocyte globulin

Arm C: Severe Aplastic Anemia (matched related donor)

EXPERIMENTAL

Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.

Drug: AlemtuzumabDrug: FludarabineDrug: CyclophosphamideRadiation: Total Body IrradiationBiological: Stem Cell TransplantDrug: Anti-thymocyte globulin

Arm D: Dyskeratosis Congenita (DKC), PTCy platform

EXPERIMENTAL

Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.

Drug: AlemtuzumabDrug: FludarabineDrug: CyclophosphamideBiological: Stem Cell Transplant

Arm E: Severe Aplastic Anemia (SAA), PTCy platform

EXPERIMENTAL

Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.

Drug: AlemtuzumabDrug: FludarabineDrug: CyclophosphamideRadiation: Total Body IrradiationBiological: Stem Cell TransplantDrug: Anti-thymocyte globulin

Interventions

AlemtuzumabDRUG

Alemtuzumab 0.2 mg/kg IV over 2 hours on days -10 to -6 from transplant.

Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Arm C: Severe Aplastic Anemia (matched related donor)Arm D: Dyskeratosis Congenita (DKC), PTCy platformArm E: Severe Aplastic Anemia (SAA), PTCy platform
FludarabineDRUG

Fludarabine 40 mg/m2 IV over 1 hour on days -6 to -2 from transplant.

Also known as: Fludara
Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Arm C: Severe Aplastic Anemia (matched related donor)Arm D: Dyskeratosis Congenita (DKC), PTCy platformArm E: Severe Aplastic Anemia (SAA), PTCy platform
CyclophosphamideDRUG

Cyclophosphamide 50 mg/kg IV over 2 hours on day -7 from transplant.

Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Arm C: Severe Aplastic Anemia (matched related donor)Arm D: Dyskeratosis Congenita (DKC), PTCy platformArm E: Severe Aplastic Anemia (SAA), PTCy platform
Total Body IrradiationRADIATION

TBI 200 cGy as a single fraction on day -1 from transplant.

Also known as: TBI
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Arm C: Severe Aplastic Anemia (matched related donor)Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Stem Cell TransplantBIOLOGICAL

Stem cell transplant on day 0.

Also known as: HSCT
Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Arm C: Severe Aplastic Anemia (matched related donor)Arm D: Dyskeratosis Congenita (DKC), PTCy platformArm E: Severe Aplastic Anemia (SAA), PTCy platform
Anti-thymocyte globulinDRUG

ATG (Thymoglobulin - Rabbit ) 3 mg/kg IV on days -5 to -3 from stem cell transplant.

Also known as: Rabbit ATG
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)Arm C: Severe Aplastic Anemia (matched related donor)Arm E: Severe Aplastic Anemia (SAA), PTCy platform

Eligibility Criteria

Age0 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Aged 0 - 70 years
  • Acceptable hematopoeitic stem cell donor
  • Dyskeratosis Congenita (DC) with evidence of BM failure defined as:
  • requirement for red blood cell and/or platelet transfusions or
  • requirement for G-CSF or GM-CSF or erythropoietin or
  • refractory cytopenias having one of the following three
  • platelets \<50,000/uL or transfusion dependent
  • absolute neutrophil count \<500/uL without hematopoietic growth factor support
  • hemoglobin \<9g/uL or transfusion dependent
  • Diagnosis of DC with a triad of mucocutaneous features:
  • oral leukoplakia
  • nail dystrophy
  • abnormal reticular skin hyperpigmentation, or
  • Diagnosis of DC with one of the following:
  • short telomeres (under a research study)
  • +18 more criteria

You may not qualify if:

  • Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
  • Pregnant or lactating
  • Uncontrolled infection
  • Prior radiation therapy (applies to SAA patients only)
  • Diagnosis of Fanconi anemia based on DEB
  • Diagnosis of dyskeratosis congenita with advanced MDS or acute myeloid leukemia with \>30% blasts

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Dyskeratosis CongenitaAnemia, Aplastic

Interventions

Alemtuzumabfludarabinefludarabine phosphateCyclophosphamideWhole-Body IrradiationStem Cell TransplantationAntilymphocyte Serumthymoglobulin

Condition Hierarchy (Ancestors)

Congenital Bone Marrow Failure SyndromesBone Marrow Failure DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesSkin AbnormalitiesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, X-LinkedGenetic Diseases, InbornSkin Diseases, GeneticSkin DiseasesSkin and Connective Tissue DiseasesAnemia

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsRadiotherapyTherapeuticsInvestigative TechniquesCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTransplantationSurgical Procedures, OperativeImmune SeraBiological ProductsComplex Mixtures

Results Point of Contact

Title
Christen Ebens, MD, MPH
Organization
Masonic Cancer Center
ebens012@umn.edu
612-624-4511

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 10, 2014

First Posted

June 12, 2014

Study Start

January 10, 2015

Primary Completion

August 8, 2024

Study Completion

March 11, 2025

Last Updated

May 8, 2025

Results First Posted

May 8, 2025

Record last verified: 2025-05

Locations

US(1)