Sorafenib Tosylate Before and After Donor Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia
Adult Acute Myeloid Leukemia in Remission
Procedure: Bone Marrow Transplantation
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Sorafenib Tosylate
|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|
- Proportion of patients removed from the study in each cohort due to toxicity [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]Will be reported with exact binomial proportions and 95% confidence intervals. All toxicities by type and grade will be reported. The proportion of patients with graft failure in each cohort will also be reported with exact binomial proportions and 95% confidence intervals.
- Change in FLT3 suppression by PIA and western blotting [ Time Frame: Baseline to day 365 ] [ Designated as safety issue: No ]Box plots will be used.
- Change in MRD by flow cytometry [ Time Frame: Baseline to day 365 ] [ Designated as safety issue: No ]Box plots will be used.
- 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 ]Standard life table methods with Kaplan-Meier (KM) plots will be used to analyze DFS. Reported with 90% confidence intervals overall and by cohort.
- OS [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Standard life table methods with KM plots will be used to analyze OS. Reported with 90% confidence intervals overall and by cohort.
- Pharmacodynamic parameters of sorafenib tosylate [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]Samples will be collected to assess sorafenib tosylate and the N-oxide metabolite (total and unbound) exposure to correlate with pharmacodynamic endpoints using non-parametric statistics.
- Changes in T-regulatory cell population [ Time Frame: Baseline to 2 years post-transplant ] [ Designated as safety issue: No ]Regression modeling of subdistribution functions in competing risks by Gray's method will be conducted to examine how changes in immunologic parameters are associated with subsequent development of GVHD. An appropriate transformation will be used to normalize the data. Differences between pre- and post-transplantation will be explored using methods appropriate for paired data. Patterns of change in marker values over time may also be explored using appropriate modeling.
|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/or transplant and no more than 120 days after transplant continuing for up to 2 years after transplant in the absence of disease progression or unacceptable toxicity.
Procedure: Bone Marrow Transplantation
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Sorafenib Tosylate
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. Non-relapse mortality (NRM) is defined, as death in the absence of competing risks, relapse or progression of disease.
IV. Survival without relapse or death (disease-free survival [DFS]) or without death (overall survival [OS]) will be determined and presented as Kaplan-Meier estimates at 1 and 2 years post-transplant.
V. Patients will be evaluated for chronic graft versus host disease (GVHD) both as described in the National Institute of Health (NIH) consensus project guidelines and by conventional criteria.
I. Patients will undergo serial examinations of bone marrow during the maintenance treatments evaluating minimal residual disease (MRD) by flow cytometry and fms-related tyrosine kinase 3 (FLT3) suppression by western blot analysis and plasma inhibitory assay (PIA). Exploratory analysis of T-regulatory cell populations for correlation with the development of GVHD.
OUTLINE: This is a dose-escalation study.
Patients receive sorafenib tosylate orally (PO) twice daily (BID) beginning at least 30 days after completion of induction therapy and/or transplant but no more than 120 days after transplant continuing for up to 2 years after transplant in the absence of disease progression or unacceptable toxicity.
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 Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Keith W. Pratz 410-502-7726 email@example.com|
|Principal Investigator: Keith W. Pratz|
|University of Maryland/Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Ashkan Emadi 410-328-2596 firstname.lastname@example.org|
|Principal Investigator: Ashkan Emadi|
|Principal Investigator:||Keith Pratz||Johns Hopkins University/Sidney Kimmel Cancer Center|