Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
Condition: Histiocytosis, Langerhans-cell
MeSH terms: Histiocytosis, Langerhans-Cell; Histiocytosis
Intervention: alemtuzumab; fludarabine phosphate; melphalan; stem cell transplantation
Intervention description: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.; Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3. (dose adjust if age <12 months); Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months); Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Melphalan; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Healthy volunteers: No
Keywords: childhood Langerhans cell histiocytosis

Summary:

      RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as
      fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's
      immune system from rejecting the donor's stem cells and helps stop the growth of abnormal
      cells. When the healthy stem cells from a donor are infused into the patient they may help
      the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
      Sometimes the transplanted cells from a donor can make an immune response against the body's
      normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may
      stop this from happening.

      PURPOSE: This phase II trial is studying how well giving alemtuzumab together with
      fludarabine and melphalan followed by a donor stem cell transplant works in treating young
      patients with resistant Langerhans cell histiocytosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed Langerhans cell histiocytosis (LCH) by demonstration of CD1a
             positivity or Birbeck granules in lesions

          -  Considered poor-risk, defined as multisystem disease with involvement of one or more
             risk organs (i.e., liver, spleen, lungs, and/or hematopoietic system)

               -  No isolated "lung only" LCH

          -  Progressive disease after one of the following treatments:

               -  LCH-III protocol or other standard LCH-directed therapies

               -  At least 1 course of the current salvage protocol (i.e., LCH-2 2005) or similar
                  therapy (e.g., cytosine arabinoside or cladribine-based regimens)

          -  HLA-matched related or unrelated donor OR unrelated umbilical cord blood (UCB)
             available

               -  1 locus mismatch for donor allowed

               -  Up to 2 loci mismatch for unrelated UCB allowed

          -  Any hematologic status (transfusion support allowed)

          -  Adequate hepatic, renal, cardiac, and pulmonary function to undergo reduced-intensity
             hematopoietic cell transplantation (RI-HCT) including the following:

               -  Transaminases < 5 times upper limit of normal (ULN)

               -  Bilirubin < 3 times ULN (unless secondary to hepatic LCH)

               -  Creatinine ≤ 2 mg/dL (adults) (if creatinine > 1.2 OR history of renal
                  dysfunction, must have estimated creatinine clearance > 40 mL/min)

               -  Creatinine clearance > 40 mL/min (pediatrics)

               -  Glomerular filtration rate ≥ 50mL/min

          -  Negative pregnancy test

        Exclusion Criteria:

          -  Decompensated congestive heart failure, uncontrolled arrhythmia, or left ventricular
             ejection fraction ≥ 35%

          -  Pulmonary failure (i.e., requiring mechanical ventilation) unless secondary to active
             underlying LCH

          -  Isolated liver sclerosis or pulmonary fibrosis unless secondary to active underlying
             LCH

          -  Uncontrolled active life-threatening infection

          -  Pregnant or nursing

          -  Less than 4 weeks after last attempted salvage chemotherapy treatment

          -  Other concurrent chemotherapy agents (e.g., methotrexate) during entire
             transplantation period up to day 100 post-transplantation