Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
N/A
N/A
Both
Histiocytosis, Langerhans-cell
Trial Information
Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Description:
Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.
Outcome Time Frame:
Year 1, Year 3
Safety Issue:
No
Principal Investigator
Angela Smith
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
2007UC002
NCT ID:
NCT00618540
Start Date:
January 2007
Completion Date:
August 2013
Related Keywords:
- Histiocytosis, Langerhans-cell
- childhood Langerhans cell histiocytosis
- Histiocytosis
- Histiocytosis, Langerhans-Cell
Name | Location |
|---|---|
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
