Sorafenib and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome - Full Text View

Sponsored by:	National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00516828

Purpose

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
Leukemia Myelodysplastic Syndromes	Drug: cytarabine Drug: sorafenib tosylate Procedure: biopsy Procedure: laboratory biomarker analysis Procedure: mutation analysis	Phase I Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine Cytarabine hydrochloride Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Recommended phase II dose of sorafenib tosylate when given in combination with cytarabine (Phase I) [ Designated as safety issue: Yes ]
Dose-limiting toxicity (Phase I) [ Designated as safety issue: Yes ]
Complete remission (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall response rate (complete and partial response) (Phase II) [ Designated as safety issue: No ]
Time to progression (Phase II) [ Designated as safety issue: No ]
Overall survival (Phase II) [ Designated as safety issue: No ]
Transfusion dependence (Phase II) [ Designated as safety issue: No ]
Toxicity (Phase II) [ Designated as safety issue: Yes ]

Estimated Enrollment:	47
Study Start Date:	July 2007
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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.
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.

PROJECTED ACCRUAL: A total of 47 will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Acute myeloid leukemia (AML) by FAB criteria*
- High-risk myelodysplastic syndromes defined as IPSS category of intermediate-2 or greater NOTE: *By morphology and routine histochemistry and confirmed, when possible, by flow cytometric analysis of surface immunophenotype; co-expression of lymphoid markers permitted
Must be considered unsuitable for intensive chemotherapy regimens
No documented CNS involvement

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

At least 2 days since prior hydroxyurea
No other prior chemotherapy
No concurrent oral chemotherapy (e.g., hydroxyurea) to control rapidly rising peripheral blood counts or complications (e.g., bone pain)
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
No other concurrent investigational drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516828

Locations

Canada, Nova Scotia
Nova Scotia Cancer Centre	Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: David A. MacDonald 902-473-3596
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre	Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Brian Leber 905-521-2100
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Joseph Brandwein 416-946-2824
Canada, Quebec
McGill Cancer Centre at McGill University	Recruiting
Montreal, Quebec, Canada, H2W 1S6
Contact: Sarit Assouline 514-340-8207

Sponsors and Collaborators

National Cancer Institute of Canada

Investigators

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

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000560975, CAN-NCIC-IND186
Study First Received:	August 14, 2007
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00516828
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Myelodysplastic syndromes
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Acute myelogenous leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia

Preleukemia
Neoplasm Metastasis
Acute myeloid leukemia, adult
Congenital Abnormalities
Bone Marrow Diseases
Sorafenib
Acute myelocytic leukemia
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Disease
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Protein Kinase Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009