Sorafenib and Low Dose Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

This study has been completed.
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group ) Identifier:
First received: August 14, 2007
Last updated: October 5, 2015
Last verified: July 2012

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.

Condition Intervention Phase
Myelodysplastic Syndromes
Drug: cytarabine
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by Canadian Cancer Trials Group:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 21
Study Start Date: July 2007
Study Completion Date: January 2013
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: cytarabine
subcutaneously twice daily from Day 1 to 10

Detailed Description:


  • 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.


Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Diagnosis of 1 of the following:

    • Acute myeloid leukemia (AML) by FAB criteria (By morphology and routine histochemistry and confirmed, when possible, by flow cytometric analysis of surface immunophenotype; co-expression of lymphoid markers permitted)
    • High-risk myelodysplastic syndromes defined as IPSS category of intermediate-2 or greater
  • Must be considered unsuitable for intensive chemotherapy regimens
  • No documented CNS involvement


  • ECOG performance status 0-2
  • AST and ALT ≤ 2 times upper limit of normal (ULN)
  • Bilirubin normal
  • Creatinine ≤ 1.2 times ULN OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ carcinoma of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
  • No upper gastrointestinal or other conditions that would preclude compliance with or administration of oral medication
  • No serious illness or medical condition that would not permit the patient to be managed according to the protocol, including any of the following:

    • History of significant neurologic or psychiatric disorder that would impair the ability to obtain consent
    • Active, uncontrolled, serious infections
    • Active peptic ulcer disease
    • Evidence of bleeding diathesis
  • No myocardial infarction within the past 6 months
  • No congestive heart failure
  • No unstable angina
  • No active cardiomyopathy or unstable ventricular arrhythmia
  • No poorly controlled hypertension (e.g., systolic BP ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg)
  • No known hypersensitivity to the study drugs or their components
  • No preexisting hypothyroidism prior to enrollment unless patient is euthyroid on medication
  • No neuropathy ≥ grade 2


  • At least 2 days since prior hydroxyurea
  • No other prior chemotherapy
  • No concurrent therapeutic doses (≥ 2 mg/day) of anticoagulants (e.g., warfarin)

    • Doses of up to 2 mg/day given for prophylaxis of thrombosis are accepted provided INR is ≤ 1.5
  • No other concurrent experimental drugs or anticancer therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00516828

Canada, Nova Scotia
QEII Health Sciences Center
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
NCIC Clinical Trials Group
Study Chair: Brian Leber, MD, FRCPC McMaster Children's Hospital at Hamilton Health Sciences
Study Chair: David A. MacDonald, MD Nova Scotia Cancer Centre
  More Information

Macdonal DA, Assouline SE, Brandwein J, Kamel-Reid S, Eisenhauer EA, Couban S, Foo A, Leber B. Phase I/II study of low-dose cytarabine with sorafenib as first-line therapy of elderly patients with AML or high-risk myelodysplastic syndrome. J Clin Oncology 28[15s, abstr 6564]. 2010.

Responsible Party: Canadian Cancer Trials Group ( NCIC Clinical Trials Group ) Identifier: NCT00516828     History of Changes
Other Study ID Numbers: I186  CAN-NCIC-IND186  CDR0000560975 
Study First Received: August 14, 2007
Last Updated: October 5, 2015
Health Authority: Canada: Health Canada

Keywords provided by Canadian Cancer Trials Group:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
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)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Myeloid
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protein Kinase Inhibitors processed this record on May 25, 2016