Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

• Status: Terminated
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Alemtuzumab; Fludarabine; Fludarabine phosphate; Melphalan; Vidarabine

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