Clinical trial NCT02512679 (phase 2, status: terminated)
Conditions: stem cell transplantation, bone marrow transplantation, peripheral blood stem cell transplantation, allogeneic transplantation, genetic diseases, thalassemia, pediatrics, diamond-blackfan anemia, combined immune deficiency, wiskott-aldrich syndrome, chronic granulomatous disease, x-linked lymphoproliferative disease, metabolic diseases
ICD codes: D56.0, D56.1, D56.3, D56.9, D56.2, D56.5, D57.40, Z86.39, O99.280, O99.281, O99.282, O99.283, O99.284, O99.285
Drugs: cyclophosphamide dose level 1, cyclophosphamide dose level 2, cyclophosphamide dose level 3, cyclophosphamide dose level 4
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, ClCCN(CCCl)P1(=O)NCCCO1, ClCCN(CCCl)P1(=O)NCCCO1, ClCCN(CCCl)P1(=O)NCCCO1
Reason stopped: 
    optimal dose obtained for engraftment and minimizing toxicity
  
Eligibility criteria:

        Inclusion Criteria:

          -  All patients with lethal or sublethal genetic lymphohematological disease (such as
             Hemaphagocytic lymphohistiocytosis (HLH) / Familial Erythrophagocytic
             Lymphohistiocytosis (FEL), Hurler's Syndrome, Hunter's Syndrome, Kostmann's Syndrome,
             Blackfan-Diamond Anemia, Chronic granulomatous Disease (CGD), Red Cell Aplasia, CID,
             Sickle Cell Anemia, Thalassemia, Adreno-leukodystrophy, metachromatic leukodystrophy,
             Wiskott-Aldrich Syndrome, X-Linked Lymphoproliferative Disease (XLD), Metabolic
             diseases affecting hematopoiesis, but not limited to), who are candidates for
             allogeneic transplantation for their disease and have a histocompatible sibling or
             related donor, ages 0 to 21 years, will be candidates for this study protocol. The
             suitable related donor is a 10/10 or 9/10 allele Human Leukocyte Antigen (HLA) match
             with the patient. All patients who have previously had serious life- threatening
             events due to disease process may be included in the study. Patients must have
             adequate physical function and vital organ function to tolerate transplant procedure,
             as measured by:

          -  Cardiac: Shortening fraction >26% or left ventricular ejection fraction at rest must
             be > 40%.

          -  Hepatic: Bilirubin, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase
             (AST) < 3x upper limit of normal (as per local laboratory) for age (with the exception
             of isolated hyperbilirubinemia due to Gilbert's syndrome).

          -  Renal: Serum creatinine < 2x upper limit of normal for age or if serum creatinine
             elevated beyond normal range patient must have creatinine Clearance or Glomerular
             filtration rate (GFR) >50% lower limit of normal for age.

          -  Pulmonary: Forced expiratory volume (FEV)1, Forced Vital Capacity (FVC), and Diffusing
             Lung Capacity for Carbon Monoxide (DLCO) (corrected for Hgb) > 50% predicted. For
             patients where pulse oximetry is performed, O2 saturation > 92%

          -  Evaluation of iron status in patients who have received more than 12 red cell
             transfusions. Measurements of serum ferritin levels and MRI of the liver and heart
             tissue will evaluate the iron stores. If high iron load is identified in these organs
             further evaluation will be done to determine the suitability as transplant recipient.
             Should these studies indicate that chelation is necessary the following should apply:
             That the treating hematologist will provide the specific chelation type and timing.
             Evaluation of organ iron load will be part of the HSCT work-up and if high iron load
             is identified then the BMT team will work with the hematologist attending in
             developing a plan for the patient.

        Exclusion Criteria:

          -  Karnofsky performance status < 70%, or Lansky < 40% for patients < 16 years old.

          -  Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet
             clinical symptoms progress).

          -  Seropositivity for the human immunodeficiency virus (HIV).

          -  Acute active hepatitis.

          -  Diagnosis of end-organ dysfunction that precludes the ability to tolerate the
             transplant procedure.

          -  Patients with a diagnosis of Fanconi Anemia are excluded.