Sorafenib and Low Dose Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
This study has been completed.
Sponsor:
NCIC Clinical Trials Group
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00516828
First received: August 14, 2007
Last updated: January 10, 2013
Last verified: July 2012
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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 |
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 NCIC Clinical 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:
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. 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.
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 (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
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00516828
Locations
| 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
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
Additional Information:
No publications provided
| Responsible Party: | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00516828 History of Changes |
| Other Study ID Numbers: | I186, CAN-NCIC-IND186, CDR0000560975 |
| Study First Received: | August 14, 2007 |
| Last Updated: | January 10, 2013 |
| Health Authority: | Canada: Health Canada |
Keywords provided by NCIC Clinical 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 Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Cytarabine Sorafenib Antimetabolites, Antineoplastic |
Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Protein Kinase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013