Treosulfan/Fludarabine/Low Dose TBI as a Preparative Regimen for Children With AML/MDS Undergoing Allo HCT
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|ClinicalTrials.gov Identifier: NCT01772953|
Recruitment Status : Completed
First Posted : January 21, 2013
Last Update Posted : October 12, 2016
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS)||Drug: Treosulfan||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Treosulfan/Fludarabine/Low Dose Total Body Irradiation as a Preparative Regimen for Children With AML/MDS Undergoing Allogeneic Hematopoietic Cell Transplantation|
|Study Start Date :||September 2013|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
Experimental: treosulfan, fludarabine and low-dose TBI prep regimen
Treosulfan: 10-14 g/m2/day IV over 120 minutes on days -6, -5 and -4. Treosulfan will be administered prior to fludarabine on days -6 to -4 to facilitate PK testing.
Fludarabine: 30 mg/m2 IV for patients > 10 kg (or 1 mg/kg IV for patients < 10 kg) once daily per institutional infusion standards on days -6 through -2 for a total dose of 150 mg/m2 (or 5 mg/kg).
A single fraction of 200 cGy TBI will be administered on day -1. Stem cell infusion on day 0
This is a phase II, open-label, nonrandomized, prospective study of a preparative regimen consisting of treosulfan, fludarabine and low-dose total body irradiation (TBI) for children with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT).
- The primary endpoint will be overall survival (OS) at one year [ Time Frame: 1 year ]The primary objective of this study is to determine the safety and preliminary efficacy of a transplant preparative regimen consisting of treosulfan, fludarabine and low-dose TBI for children with AML and MDS. The primary endpoint will be overall survival (OS) at one year.
- Pharmacokinetic (PK) profile of Treosulfan in children < 40 kg [ Time Frame: 1 year ]Drug plasma concentrations will be determined by: Cmax; half lives (t1/2); area under the curve (AUC); volumes of distribution (V); clearances (CL); mean residence times (MRT)
- Non-Relapse Mortality [ Time Frame: 1 year ]The event is death in continuous remission treating relapse as the competing risk. Patients alive and in remission at the time of last observation will be censored.
- Disease-Free Survival [ Time Frame: 1 year ]Disease-free survival is defined as the minimum time interval from transplant to relapse/recurrence of disease, to death or to last follow-up.
- Neutrophil Engraftment [ Time Frame: 1 year ]Neutrophil engraftment is defined as achieving a donor derived absolute neutrophil count (ANC) ≥ 500/μL for three consecutive measurements on different days. The first of the three days will be designated as the time to neutrophil engraftment.
- Donor Chimerism [ Time Frame: 1 year ]Peripheral blood chimerism (% of donor chimerism) in whole blood or fractions sorted for T-cell and myeloid subsets (CD3 and CD33) will be described on days 28, 42, 100, 180 and 365.
- Acute graft-versus-host disease (GVHD) [ Time Frame: 1 year ]Incidences of grade II - IV and III - IV acute GVHD at days 42, 100, 180 and 365 will be graded according to the BMT CTN Manual of Procedures
- Relapse [ Time Frame: 1 year ]Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of AML or MDS consistent with pre-transplant features. The event for this endpoint is the time interval from transplant to relapse/recurrence of disease or to last follow-up. Death in remission is considered a competing risk.
- Primary graft failure [ Time Frame: 1 Year ]
This endpoint will be evaluated separately for bone marrow/peripheral blood and cord blood.
Primary graft failure is defined as lack of donor-derived neutrophil engraftment by 56 days. This time point was chosen to adjust for potential differences in time to engraftment that may be observed in cord blood vs. marrow/PBSC recipients. This outcome will be evaluated separately for bone marrow/peripheral blood and cord blood based on neutrophil count and peripheral blood chimerism obtained on day 42 ± 14. Relapse and death prior to neutrophil engraftment are considered competing risks for the endpoint of primary graft failure.
- Platelet engraftment of > 20,000/μL and >50,000/μL [ Time Frame: 1 Year ]Time to platelet engraftment is defined as the first day of a minimum of three consecutive measurements on different days such that the patient has achieved a platelet count > 20,000/μL and > 50,000/μL with no platelet transfusions in the preceding seven days. The first day of the three measurements will be designated as the day of platelet engraftment.
- Chronic graft-versus-host disease (GVHD) [ Time Frame: 1 Year ]Incidence of chronic GVHD on days 100, 180 and 365 will be scored according to the BMT CTN MOP
- Secondary graft failure [ Time Frame: 1 year ]Secondary graft failure is defined as initial donor-derived neutrophil engraftment followed by subsequent decline in ANC to < 500/μL for three consecutive measurements on different days, and unresponsive to growth factor therapy, with loss of donor chimerism to < 50% donor CD3 in peripheral blood.
- Primary cause of death [ Time Frame: 1 year ]Primary cause of death will be classified as: Relapse/Primary disease; GVHD; Infection; Organ Toxicity; Other
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01772953
|Study Chair:||Eneida Nemecek, MD||Doernbecher Children's Hospital, Oregon Health & Science University|
|Study Chair:||Colleen Delaney, MD||Seattle Children's Hospital, Fred Hutchinson Cancer Research Center|