Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia

Aplastic Anemia Clinical Trial

Official title:

Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02162420
• Other study ID #: 2013OC127
• Secondary ID: MT2013-34C
• Status: Recruiting
• Phase: N/A
• Start date: January 10, 2015
• Est. completion date: July 2026

Study information

• Verified date: January 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Timothy Krepski
• Phone: 612-273-2800
• Email: tkrepsk1[@]fairview.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia
• Dyskeratosis Congenita

Intervention

Drug:
• Alemtuzumab
Alemtuzumab 0.2 mg/kg IV over 2 hours on days -10 to -6 from transplant.
• Fludarabine
Fludarabine 40 mg/m2 IV over 1 hour on days -6 to -2 from transplant.
• Cyclophosphamide
Cyclophosphamide 50 mg/kg IV over 2 hours on day -7 from transplant.

Radiation:
• Total Body Irradiation
TBI 200 cGy as a single fraction on day -1 from transplant.

Biological:
• Stem Cell Transplant
Stem cell transplant on day 0.

Drug:
• Anti-thymocyte globulin
ATG (Thymoglobulin - Rabbit ) 3 mg/kg IV on days -5 to -3 from stem cell transplant.

Locations

Country	Name	City	State
United States	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of neutrophil engraftment	Incidence of neutrophil engraftment by day 42.	Day 42
Primary	Incidence of platelet engraftment	Incidence of platelet engraftment at 1 year	1 year
Secondary	Incidence of regimen related mortality	Incidence of regimen related mortality by day 100.	Day 100
Secondary	Incidence of acute graft-versus-host disease	Incidence of acute graft-versus-host disease by day 100.	Day 100
Secondary	Incidence of chronic graft-versus-host disease	Incidence of chronic graft-versus-host disease by 6 months	6 Months
Secondary	Incidence of chronic graft-versus-host disease	Incidence of chronic graft-versus-host disease by 1 year	1 Year
Secondary	Incidence of secondary malignancies	Incidence of secondary malingancies	1 Year