Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita

Status: Recruiting
Phase: Phase 2
DFCI Protocol ID: 16-294

Dyskeratosis congenita is a disease that affects numerous parts of the body, most typically causing failure of the blood system. Lung disease and a predisposition to cancer are also frequent causes of illness and death. Bone marrow transplantation (BMT) can cure the blood system but can make the lung disease and cancer predisposition worse, because of agents such as alkylators and radiation that are typically used in the procedure. Based on the biology of DC, we hypothesize that it may be possible to avoid these agents in patients with DC, and still have a successful BMT. In this protocol we will test whether a regimen that avoids alkylators and radiation can permit successful BMT without compromising survival in patients with DC.

Conducting Institutions:

Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

Suneet Agarwal, MD, PhD, Children's Hospital Boston

Site-responsible Investigators:


Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  Bone marrow cellularity: hypocellular for age

  -  Moderate or severe aplastic anemia defined by one of the following: peripheral blood
     neutrophils < 0.5 x 10^9/L; platelets < 30 x 10^9/L or platelet transfusion
     dependence; reticulocytes < 50 x 10^9/L in anemic patients or red cell transfusion

  -  Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin
     pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence
     of two or more associated features; OR a pathogenic mutation in DKC1,TERC, TERT,
     NOP10, NHP2, TCAB1, TINF2, CTC1 as reported by a CLIA-approved laboratory; OR
     age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes as reported
     by a CLIA-approved laboratory; OR Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome

  -  Availability of a related or unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C,
     and DRB1.

  -  Patient and/or legal guardian must be able to sign informed consent.

  -  Matched unrelated donor must consent to provide a marrow allograft.

  -  Diagnosis of Fanconi anemia must be excluded by mitomycin C or diepoxybutane
     chromosomal breakage testing on peripheral blood at a CLIA-approved laboratory (not
     required for patients with a genetic mutation consistent with DC)

  -  Adequate renal function with glomerular filtration rate equal to or greater than 30
     ml/min/1.73 m2

Exclusion Criteria:

  -  Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow

  -  Karnofsky/Lansky performance status < 40%.

  -  Uncontrolled bacterial, viral or fungal infections.

  -  Positive test for the human immunodeficiency virus (HIV).

  -  Pregnancy or breastfeeding.

  -  Known severe or life-threatening allergy or intolerance to fludarabine, alemtuzumab,
     cyclosporine, or mycophenolate mofetil.

  -  Positive patient anti-donor HLA antibody, which is deemed clinically significant.

  -  Prior allogeneic marrow or stem cell transplantation.

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