Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia

University of Minnesota (UMN)

Status: Completed

Conditions: Dyskeratosis Congenita; Aplastic Anemia

Treatments: Biological: Stem Cell Transplant; Drug: Alemtuzumab; Drug: Fludarabine; Drug: Anti-thymocyte globulin; Radiation: Total Body Irradiation; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02162420

2013OC127

MT2013-34C (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 61 patients

Sex: All

Ages: Under 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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61 participants in 5 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Alemtuzumab

Biological: Stem Cell Transplant

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

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Radiation: Total Body Irradiation

Drug: Anti-thymocyte globulin

Drug: Fludarabine

Drug: Alemtuzumab

Biological: Stem Cell Transplant

Arm C: Severe Aplastic Anemia (matched related donor)

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Radiation: Total Body Irradiation

Drug: Anti-thymocyte globulin

Drug: Fludarabine

Drug: Alemtuzumab

Biological: Stem Cell Transplant

Arm D: Dyskeratosis Congenita (DKC), PTCy platform

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Alemtuzumab

Biological: Stem Cell Transplant

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

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Radiation: Total Body Irradiation

Drug: Anti-thymocyte globulin

Drug: Fludarabine

Drug: Alemtuzumab

Biological: Stem Cell Transplant