Clinical trial NCT02162420: Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
Official title: Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dyskeratosis Congenita
Aplastic Anemia
Keywords: severe aplastic anemia
Hematopoietic Stem Cell Transplant
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2014-06-12
Enrollment: 61
Sex: ALL
Minimum age (years): 0
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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)
  * mutation in telomerase holoenzyme (DKC1, TERT, TERC, NOP10, NHP2, TCAB1)
  * mutation in shelterin complex (TINF2)
  * mutation in telomere-capping complex (CTC1)
* Severe Aplastic Anemia (SAA) primary transplant with evidence of BM failure:

  * Refractory cytopenia defined by bone marrow cellularity \<50% (with \< 30% residual hematopoietic cells)
* Diagnosis of SAA with refractory cytopenias having one of the following three:

  * platelets \<20,000/uL or transfusion dependent
  * absolute neutrophil count \<500/uL without hematopoietic growth factor support
  * absolute reticulocyte count \<20,000/uL
* Severe Aplastic Anemia (SAA) requiring a 2nd transplant

  * Graft failure as defined by blood/marrow chimerism of \< 5%
* Early myelodysplastic features
* With or without clonal cytogenetic abnormalities
* Adequate organ function defined as:

  * cardiac: left ventricular ejection fraction ≥ 35% with no evidence of decompensated heart failure
  * pulmonary: DLCO ≥30% predicted, no supplemental oxygen requirement
  * renal: Glomerular filtration rate (GFR) ≥30% predicted
* Voluntary written consent

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence of Neutrophil Engraftment
timeFrame: Day 42
measure: Incidence of Platelet Engraftment
timeFrame: 1 year
Secondary outcomes:
measure: Incidence of Regimen Related Mortality
timeFrame: Day 100
measure: Incidence of Acute Graft-versus-host Disease
timeFrame: Day 100
measure: Incidence of Chronic Graft-versus-host Disease
timeFrame: 6 Months
measure: Incidence of Chronic Graft-versus-host Disease
timeFrame: 1 Year
measure: Incidence of Secondary Malignancies
timeFrame: 1 Year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
Study officials:
References: