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Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02162420
Recruitment Status : Recruiting
First Posted : June 12, 2014
Last Update Posted : January 26, 2023
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Description
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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.

Condition or disease Intervention/treatment Phase
Dyskeratosis Congenita Aplastic Anemia Drug: Alemtuzumab Drug: Fludarabine Drug: Cyclophosphamide Radiation: Total Body Irradiation Biological: Stem Cell Transplant Drug: Anti-thymocyte globulin Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
Actual Study Start Date : January 10, 2015
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment Plan for Dyskeratosis Congenita
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, and total body irradiation, followed by stem cell transplant for the treatment of dyskeratosis congenita.
 Drug: Alemtuzumab
Alemtuzumab 0.2 mg/kg IV over 2 hours on days -10 to -6 from transplant.

Drug: Fludarabine
Fludarabine 40 mg/m2 IV over 1 hour on days -6 to -2 from transplant.
Other Name: Fludara

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

Biological: Stem Cell Transplant
Stem cell transplant on day 0.
Other Name: HSCT
Experimental: Treatment for Severe Aplastic Anemia
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
 Drug: Fludarabine
Fludarabine 40 mg/m2 IV over 1 hour on days -6 to -2 from transplant.
Other Name: Fludara

Drug: 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.
Other Name: TBI

Biological: Stem Cell Transplant
Stem cell transplant on day 0.
Other Name: HSCT

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


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of neutrophil engraftment [ Time Frame: Day 42 ]
    Incidence of neutrophil engraftment by day 42.

  2. Incidence of platelet engraftment [ Time Frame: 1 year ]
    Incidence of platelet engraftment at 1 year


Secondary Outcome Measures :
  1. Incidence of regimen related mortality [ Time Frame: Day 100 ]
    Incidence of regimen related mortality by day 100.

  2. Incidence of acute graft-versus-host disease [ Time Frame: Day 100 ]
    Incidence of acute graft-versus-host disease by day 100.

  3. Incidence of chronic graft-versus-host disease [ Time Frame: 6 Months ]
    Incidence of chronic graft-versus-host disease by 6 months

  4. Incidence of chronic graft-versus-host disease [ Time Frame: 1 Year ]
    Incidence of chronic graft-versus-host disease by 1 year

  5. Incidence of secondary malignancies [ Time Frame: 1 Year ]
    Incidence of secondary malingancies


Eligibility Criteria
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Ages Eligible for Study:   0 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02162420


Contacts
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Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org

Locations
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United States, Minnesota
University of Minnesota Medical Center, Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Timothy Krepski    612-273-2800    tkrepsk1@fairview.org   
Principal Investigator: Jakub Tolar, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Jakub Tolar, MD University of Minnesota
More Information
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02162420    
Other Study ID Numbers: 2013OC127
MT2013-34C ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
First Posted: June 12, 2014    Key Record Dates
Last Update Posted: January 26, 2023
Last Verified: January 2023
Keywords provided by Masonic Cancer Center, University of Minnesota:
severe aplastic anemia
Hematopoietic Stem Cell Transplant
Additional relevant MeSH terms:
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Anemia
Anemia, Aplastic
Dyskeratosis Congenita
Hematologic Diseases
Bone Marrow Failure Disorders
Bone Marrow Diseases
Congenital Bone Marrow Failure Syndromes
Skin Abnormalities
Congenital Abnormalities
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Cyclophosphamide
 Fludarabine
Alemtuzumab
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological