Clinical trial NCT00618540
Conditions: Histiocytosis, Langerhans-cell
Keywords: childhood Langerhans cell histiocytosis
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2007-01-01; Completion date: 2013-05-01
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
OBJECTIVES:

Primary

* To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT).

Secondary

* To determine day 100 transplantation-related mortality.
* To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT.
* To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD).
* To determine the incidence of chronic GVHD.

OUTLINE: This is a multicenter study.

* Non-myeloablative conditioning: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -4, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and melphalan IV over 15-30 minutes on day -2. Some patients may receive anti-thymocyte globulin IV on days -6 to -2 instead of alemtuzumab.
* Graft-versus-host disease prophylaxis and immunosuppression: Patients receive cyclosporine A (CSA) IV or orally 2-3 times daily beginning on day -3 and continuing until day 50 post transplantation, followed by a taper over 8 weeks in the absence of GVHD or donor lymphocyte infusion given for decreasing donor chimerism. Patients with mismatched donors (any source) and those receiving peripheral blood stem cells also receive mycophenolate mofetil (MMF) IV or orally 2-3 times daily beginning on day -3 and continuing to day 30 or 7 days after engraftment, whichever day is later, in the absence of GVHD. In patients with acute GVHD requiring systemic therapy, Mycophenolate mofetil (MMF) may be stopped 7 days after initiation of systemic therapy.
* Allogeneic hematopoietic stem cell infusion: Patients undergo infusion of bone marrow (preferred) or peripheral blood stem cells on day 0. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 8 and continuing until blood counts recover for 2 consecutive days.
* Donor lymphocyte infusion (DLI): Patients with mixed chimerism (i.e., \< 95% donor) and those with \< 50% donor T-cell engraftment at any engraftment assessment time point are eligible for DLI, in the absence of GVHD. If mixed chimerism persists, escalating doses of CD3-positive lymphocytes are administered every 3-4 weeks, in the absence of GVHD.

After completion of study therapy, patients are followed from engraftment through day 100, and then at 6 months, 1 year, and annually thereafter for 2-5 years.

Arms: arm 1: Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.
Interventions: intervention 1: alemtuzumab intervention 2: fludarabine phosphate intervention 3: melphalan intervention 4: stem cell transplantation
Intervention descriptions: intervention 1: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4. intervention 2: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3. (dose adjust if age \<12 months) intervention 3: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age \<12 months) intervention 4: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Protocol documents: