Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
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.
Drug: fludarabine phosphate
Procedure: stem cell transplantation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis|
- Overall Survival [ Time Frame: Year 1, Year 3 ] [ Designated as safety issue: No ]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.
- Disease-free Survival at 12 Months Post Transplantation [ Time Frame: Year 1 ] [ Designated as safety issue: No ]
This outcome is defined as survival with resolution of LCH at 12 months post transplant.
Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events.
Those who survive with resolution of disease are censored at the date of last contact.
- Transplantation-related Death [ Time Frame: Day 100 ] [ Designated as safety issue: No ]Count of patients who died by day 100 related to the transplantation.
- Neutrophil Engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]Incidence of neutrophil recovery and donor chimerism at Day 100.
- Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD) [ Time Frame: Day 100 and Month 6 ] [ Designated as safety issue: No ]The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
- Incidence of Chronic GVHD [ Time Frame: Day 100 and Month 6 ] [ Designated as safety issue: No ]Occurrence of symptoms in any organ system fulfilling the criteria of limited or extensive chronic GvHD (Appendix III), among patients surviving > 90 days with evidence of engraftment. Patients without chronic GvHD will be censored at time of death or last follow-up.
- Platelet Engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]Incidence of platelet recovery and donor chimerism at Day 100.
- Incidence of Grade III-IV Acute Graft-versus-host-disease (GVHD) [ Time Frame: Day 100 and Month 6 ] [ Designated as safety issue: No ]The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
|Study Start Date:||January 2007|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.
Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.
Other Name: Campath(R)Drug: fludarabine phosphate
Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3. (dose adjust if age <12 months)
Other Name: Fludara(R)Drug: melphalan
Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)
Other Name: AlkeranProcedure: stem cell transplantation
Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation
Other Name: Stem cell transplant
- 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).
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00618540
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Angela Smith||Masonic Cancer Center, University of Minnesota|