Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
Histiocytosis, Langerhans-cell
About this trial
This is an interventional treatment trial for Histiocytosis, Langerhans-cell focused on measuring childhood 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
Sites / Locations
- Masonic Cancer Center at University of Minnesota
Arms of the Study
Arm 1
Experimental
Alemtuzumab
Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.