Sorafenib and Low Dose Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cytarabine may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving sorafenib together with cytarabine and to see how well it works in treating older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Sorafenib (BAY 43-9006) in Combination With Low Dose ARA-C (CYTARABINE) in Elderly Patients With AML or High-Risk MDS|
- Recommended phase II dose of sorafenib tosylate when given in combination with cytarabine (Phase I) [ Time Frame: 29 months ] [ Designated as safety issue: Yes ]
- Dose-limiting toxicity (Phase I) [ Time Frame: 29 months ] [ Designated as safety issue: Yes ]
- Complete remission (Phase II) [ Time Frame: 29 months ] [ Designated as safety issue: No ]
- Overall response rate (complete and partial response) (Phase II) [ Time Frame: 29 months ] [ Designated as safety issue: No ]
- Time to progression (Phase II) [ Time Frame: 29 months ] [ Designated as safety issue: No ]
- Overall survival (Phase II) [ Time Frame: 29 months ] [ Designated as safety issue: No ]
- FLT-3 ITD endpoint mutation response correlation. [ Time Frame: 29 months ] [ Designated as safety issue: No ]
- Toxicity (Phase II) [ Time Frame: 29 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2007|
|Study Completion Date:||January 2013|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Experimental: Sorafenib and Cytarabine
Cytarabine: subcutaneously twice daily from day 1 - 10. Sorafenib: Days 2-28; at the dose level assigned at registration. Sorafenib will be given orally twice daily.
subcutaneously twice daily from Day 1 to 10
- To determine the recommended dose of sorafenib tosylate and cytarabine when given in combination to elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndromes who are not suitable for intensive chemotherapy. (Phase I)
- To determine the safety, tolerability, toxicity profile, and dose-limiting toxicities in patients treated with this regimen. (Phase I)
- To estimate the efficacy (as measured by complete response rate) in patients treated with this regimen. (Phase II)
- To describe the toxic effects and overall response rate (complete and partial) in patients treated with this regimen. (Phase II)
- To evaluate potential correlates of response in translational research studies including FLT-3 internal tandem duplications and point mutations in blasts. (Phase II)
OUTLINE: This is a multicenter study.
- Phase I: Patients receive oral sorafenib tosylate twice daily on days 2-28 and cytarabine subcutaneously twice daily on days 1-10 at the dose level assigned at registration. Doses of both drugs will be escalated and the recommended doses for the combination will be determined. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who respond to treatment will receive 2 cycles after response criteria are met.
- Phase II: Patients receive sorafenib tosylate and cytarabine as in phase I at the recommended doses for the combination determined in phase I.
Bone marrow (or blood) samples are collected at baseline and at the end of each course of study treatment. Baseline samples are analyzed for mutational status of FLT-3 (i.e., internal tandem duplication [ITD] and point mutations).
After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter until progression and toxicities resolve.
|Canada, Nova Scotia|
|QEII Health Sciences Center|
|Halifax, Nova Scotia, Canada, B3H 1V7|
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|McGill University - Dept. Oncology|
|Montreal, Quebec, Canada, H2W 1S6|
|Study Chair:||Brian Leber, MD, FRCPC||McMaster Children's Hospital at Hamilton Health Sciences|
|Study Chair:||David A. MacDonald, MD||Nova Scotia Cancer Centre|