Sorafenib Tosylate Before and After Donor Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
This pilot trial studies how well sorafenib tosylate works before and after donor bone marrow transplantation in treating patients with acute myeloid leukemia. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Drug: sorafenib tosylate
Procedure: bone marrow transplantation
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Sorafenib in Patients With Acute Myeloid Leukemia as Peri-Transplant Remission Maintenance|
- Toxicity [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]All toxicities by type and grade will be reported with exact binomial proportions and 95% confidence intervals. The proportion of patients with graft failure in each cohort will also be reported with exact binomial proportions and 95% confidence intervals.
- Cumulative incidence of NRM and relapse [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Estimated by competing risks analysis using Grey's method.
- DFS [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Reported with 90% confidence intervals overall and by cohort.
- OS [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Reported with 90% confidence intervals overall and by cohort.
- Change in MRD by flow cytometry [ Time Frame: From baseline to days 28, 180, and 365 ] [ Designated as safety issue: No ]Box plots will be used.
- Change in FLT3 suppression by PIA and western blotting [ Time Frame: From baseline to on days 28, 180 and 365 ] [ Designated as safety issue: No ]Box plots will be used.
|Study Start Date:||January 2012|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate and transplant)
Patients receive sorafenib tosylate PO BID beginning at least 30 days after completion of induction therapy and continuing until 4 days prior to BMT preparative regimen. At time of engraftment but no later than 120 days after BMT, patients receive sorafenib tosylate PO BID continuously for up to 2 years in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Other Names:Procedure: bone marrow transplantation
Other Names:Other: laboratory biomarker analysis
I. Determine the toxicity and safety of incorporation of sorafenib tosylate (sorafenib) into the pre- or post-transplant maintenance setting for three types of transplants.
I. Improvement of 2 year disease free survival after bone marrow transplant by 25% based on a baseline relapse free survival at two years of 30%.
II. Secondary graft failure is defined as the decline in neutrophil count to < 500/cu mm after achieving engraftment which is unrelated to infection or drug effect (sorafenib?) and is unresponsive to stimulation by growth factors.
III. NRM is defined, as death in the absence of competing risks, relapse or progression of disease. This secondary endpoint will be characterized and presented as a cumulative incidence at day 100 and at 1 year after BMT.
IV. Survival without relapse or death (DFS) or without death (OS) will be determined and presented as Kaplan-Meier estimates at 1 and 2 years post-transplant.
V. Patients will be evaluated for chronic GVHD both as described in the NIH consensus project guidelines and by conventional criteria. The first day of chronic GVHD onset will be used to calculate cumulative incidence curves using the competing risk method. Graft failure, relapse or death without GVHD is considered competing risks for GVHD.
I. Patients will undergo serial examinations of bone marrow during the maintenance treatments evaluating MRD by flow cytometry and FLT3 suppression by western blot analysis and PIA. Samples will be collected to assess sorafenib and the N-oxide metabolite (total and unbound) exposure to correlate with pharmacodynamic endpoints.
OUTLINE: Patients are stratified according to type of transplant (myeloablative, matched, related donor vs nonmyeloablative, matched, haploidentical donor vs myeloablative, haploidentical or partially mismatched, unrelated donor).
Patients receive sorafenib tosylate orally (PO) twice daily (BID) beginning at least 30 days after completion of induction therapy and continuing until 4 days prior to bone marrow transplant (BMT) preparative regimen. At time of engraftment but no later than 120 days after BMT, patients receive sorafenib tosylate PO BID continuously for up to 2 years in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and bone marrow sample collection at baseline and periodically during treatment to determine the effect of sorafenib tosylate and its metabolites on P-ERK and P-FLT3 levels ex-vivo, presence of FLT3 target inhibition in-vivo, and MRD by PIA, polymerase chain reaction assays, western blotting, and flow cytometry.
After completion of study treatment, patients are followed up for 24 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01578109
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Keith W. Pratz 410-502-7726 firstname.lastname@example.org|
|Principal Investigator: Keith W. Pratz|
|University of Maryland/Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Ashkan Emadi 410-328-2596 email@example.com|
|Principal Investigator: Ashkan Emadi|
|Principal Investigator:||Keith Pratz||Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|