Sorafenib Tosylate Before and After Donor Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia
This pilot clinical trial studies the side effects of sorafenib tosylate 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: pharmacological study
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|
- 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.
- 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.
- Change in MRD by flow cytometry [ Time Frame: Baseline to day 365 ] [ Designated as safety issue: No ]Box plots will be used.
- 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.
- Pharmacodynamic parameters of sorafenib tosylate [ Time Frame: Days 1, 28, 60, 6 months, 1 year, and 2 years post transplant ] [ Designated as safety issue: No ]Samples will be collected to assess sorafenib and the N-oxide metabolite (total and unbound) exposure to correlate with pharmacodynamic endpoints using non-parametric statistics.
|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 for up to 2 years after transplant in the absence of disease progression or unacceptable toxicity.
Drug: sorafenib tosylate
Other Names:Procedure: bone marrow transplantation
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: 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. 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).
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 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 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|