ED-TBI Followed By Allogeneic Stem Cell Transplantation For The Treatment Of Refractory AML And Advanced MDS (ED-TBI)
Recruitment status was: Recruiting
Acute myeloid leukemia (AML) is a rapidly fatal malignancy of the bone marrow. It can be treated with chemotherapy alone, in some cases, but in the majority of cases, the only treatment that can cure the disease is an allogeneic stem cell transplant, with a cure rate of 30-40%. In another subset, the disease is less responsive to chemotherapy and in these aggressive forms, its cure rate is no better than 20% beyond 2 years, and is usually rapidly fatal within 6 months.
Therefore, for this most aggressive form of the disease, modifications to the transplant protocol are required in order to try to improve on these poor results. There are a number of areas within the transplant protocol on which modifications can be made in order to achieve these goals. These include: higher doses of chemotherapy and or radiation; alterations of the new bone marrow graft; and alterations of the immune suppression, enhancing the graft vs. leukemia effect. By focusing on one or more of these components, one might be able to enhance the anti-leukemic aspect of the treatment resulting in a more successful outcome.
One aspect the investigators, in Ottawa, have focused on is the initial intensive conditioning regimen, specifically the radiation component. It is the investigators belief that in the most resistant disease it is important to use the highest tolerable anti-leukemic treatment upfront, specifically, enhancing the radiation component of the initial conditioning regimen. Previous studies have suggested that higher doses of radiation might be more effective at eliminating the disease, however, toxicity and logistics of delivering the radiation have limited its use. Technical advances in the delivery of radiation have now permitted the safer use of high doses of radiation.
Through modifications to the transplant procedure, the investigators believe that they can deliver higher doses of radiation safely and this will translate into improved outcomes in this high-risk subgroup of patients with AML.
The goal of this study is to determine if a total dose of 18Gy ED-TBI followed by an alloHSCT for patients with refractory AML will result in an improved progression-free survival.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Extended Dose - Total Body Irradiation Followed By Allogeneic Stem Cell Transplantation For The Treatment Of Refractory Acute Leukemia And Advanced Myelodysplastic Syndrome|
- Progression-free survival [ Time Frame: 1 year post allogenic transplant ] [ Designated as safety issue: Yes ]The primary objective of this study is to determine the progression-free survival at 1 year, post alloHSCT, after ED-TBI followed by an alloHSCT for patients with refractory AML
- Engraftment [ Time Frame: Within 100 day post tranplant ] [ Designated as safety issue: Yes ]The time to neutrophil and platelet engraftment following ED-TBI and alloHSCT
- Morbidity/Mortality [ Time Frame: day 30, day 100, day 180 post tranplant ] [ Designated as safety issue: No ]
- The day 30 morbidity (frequency, severity and affected organ function) of ED-TBI
- The day 30 mortality associated with ED-TBI and alloHSCT.
- The day 100 morbidity (frequency, severity and affected organ function) of ED-TBI
- The day 100 mortality associated with ED-TBI and alloHSCT.
- The late (> 6 month and >1 year) morbidity and mortality of ED-TBI/alloHSCT
- Relapse [ Time Frame: 5 years post transplant ] [ Designated as safety issue: No ]
- Relapse rate after alloHSCT
- The pattern of relapse (blood and marrow vs. extramedullary)
- The overall survival
- GVHD [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ] [ Designated as safety issue: Yes ]Incidence and severity of acute and chronic GVHD
- Evaluation of Safety [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ] [ Designated as safety issue: Yes ]
All patients who receive at least one fraction of ED-TBI will be used in the safety analysis.
- The incidence of adverse and serious adverse events will be tabulated by, severity and relationship to the treatment.
- Adverse and serious adverse events will be monitored on an ongoing basis by the investigators.
- Adverse events will be categorized using the CTCAE v.4. Adverse events will be summarized at the following intervals post stem cell transplant: day 30, day 100, 180, 365 and 730.
- Evaluation of Efficacy [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ] [ Designated as safety issue: No ]Objective data to determine CR rate, rate of relapse, time-to-progression and overall survival will be collected and reported.
- Duration of Study [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]Approximately, 5 patients from our institution will be eligible per year. Additional patients from cooperating centers could, potentially, add another 5 patients/year. Therefore, the duration of accrual is expected to be between 2-3 years.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: 18 cGY ED-TBI
18 cGY ED-TBI followed by an allogenic done marrow transplant
Patients will receive 18Gy ED-TBI in 8 fractions of 2.25 Gy each, twice/day for 4 days. Following the final fraction of TBI and an allogeneic hematopoietic stem cell graft.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01709396
|The Ottawa Hospital - General Campus|
|Ottawa, Ontario, Canada, K1H8L6|
|Principal Investigator:||Mitchell Sabloff||The Ottawa Hospital - Ottawa Hospital Research Institute|