Back to resultsHematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
Primary Purpose
Dyskeratosis Congenita, Aplastic Anemia
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Alemtuzumab
Fludarabine
Cyclophosphamide
Total Body Irradiation
Stem Cell Transplant
Anti-thymocyte globulin
Sponsored by
About this trial
This is an interventional treatment trial for Dyskeratosis Congenita focused on measuring severe aplastic anemia, Hematopoietic Stem Cell Transplant
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
Sites / Locations
- University of Minnesota Medical Center, FairviewRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Treatment Plan for Dyskeratosis Congenita
Treatment for Severe Aplastic Anemia
Arm Description
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, and total body irradiation, followed by stem cell transplant for the treatment of dyskeratosis congenita.
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
Outcomes
Primary Outcome Measures
Incidence of neutrophil engraftment
Incidence of neutrophil engraftment by day 42.
Incidence of platelet engraftment
Incidence of platelet engraftment at 1 year
Secondary Outcome Measures
Incidence of regimen related mortality
Incidence of regimen related mortality by day 100.
Incidence of acute graft-versus-host disease
Incidence of acute graft-versus-host disease by day 100.
Incidence of chronic graft-versus-host disease
Incidence of chronic graft-versus-host disease by 6 months
Incidence of chronic graft-versus-host disease
Incidence of chronic graft-versus-host disease by 1 year
Incidence of secondary malignancies
Incidence of secondary malingancies
Full Information
NCT ID
NCT02162420
First Posted
June 10, 2014
Last Updated
January 25, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02162420
Brief Title
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 10, 2015 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyskeratosis Congenita, Aplastic Anemia
Keywords
severe aplastic anemia, Hematopoietic Stem Cell Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Plan for Dyskeratosis Congenita
Arm Type
Experimental
Arm Description
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, and total body irradiation, followed by stem cell transplant for the treatment of dyskeratosis congenita.
Arm Title
Treatment for Severe Aplastic Anemia
Arm Type
Experimental
Arm Description
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Intervention Description
Alemtuzumab 0.2 mg/kg IV over 2 hours on days -10 to -6 from transplant.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine 40 mg/m2 IV over 1 hour on days -6 to -2 from transplant.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 50 mg/kg IV over 2 hours on day -7 from transplant.
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Description
TBI 200 cGy as a single fraction on day -1 from transplant.
Intervention Type
Biological
Intervention Name(s)
Stem Cell Transplant
Other Intervention Name(s)
HSCT
Intervention Description
Stem cell transplant on day 0.
Intervention Type
Drug
Intervention Name(s)
Anti-thymocyte globulin
Other Intervention Name(s)
Rabbit ATG
Intervention Description
ATG (Thymoglobulin - Rabbit ) 3 mg/kg IV on days -5 to -3 from stem cell transplant.
Primary Outcome Measure Information:
Title
Incidence of neutrophil engraftment
Description
Incidence of neutrophil engraftment by day 42.
Time Frame
Day 42
Title
Incidence of platelet engraftment
Description
Incidence of platelet engraftment at 1 year
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Incidence of regimen related mortality
Description
Incidence of regimen related mortality by day 100.
Time Frame
Day 100
Title
Incidence of acute graft-versus-host disease
Description
Incidence of acute graft-versus-host disease by day 100.
Time Frame
Day 100
Title
Incidence of chronic graft-versus-host disease
Description
Incidence of chronic graft-versus-host disease by 6 months
Time Frame
6 Months
Title
Incidence of chronic graft-versus-host disease
Description
Incidence of chronic graft-versus-host disease by 1 year
Time Frame
1 Year
Title
Incidence of secondary malignancies
Description
Incidence of secondary malingancies
Time Frame
1 Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Timothy Krepski
Phone
612-273-2800
Email
tkrepsk1@fairview.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jakub Tolar, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Medical Center, Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timothy Krepski
Phone
612-273-2800
Email
tkrepsk1@fairview.org
First Name & Middle Initial & Last Name & Degree
Jakub Tolar, MD
12. IPD Sharing Statement
Learn more about this trial
Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
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