Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

April 27, 2015 updated by: National Cancer Institute (NCI)

Phase I Study of BAY 43-9006 (NSC 724772) in Patients With Acute Leukemias, Myelodysplastic Syndromes and Chronic Myeloid Leukemia in Blast Phase

This randomized phase I trial is studying the side effects and best dose of two different schedules of sorafenib in treating patients with refractory or relapsed acute leukemia, myelodysplastic syndromes, or blastic phase chronic myelogenous leukemia. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of sorafenib when administered in two different schedules in patients with refractory or relapsed acute leukemia, myelodysplastic syndromes, or blastic phase chronic myelogenous leukemia.

II. Determine the dose-limiting toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the clinical activity of this drug in these patients. II. Determine the biologic effect of this drug in these patients.

OUTLINE: This is a randomized, dose-escalation phase I study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral sorafenib once or twice daily on days 1-5, 8-12, and 15-19.

Arm II: Patients receive oral sorafenib once or twice daily on days 1-14.

In both arms, treatment repeats every 21 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission or partial remission after 6 months may continue therapy at the discretion of the principal investigator.

In both arms, cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 patients are treated at the MTD.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of 1 of the following: Acute myeloid leukemia (Acute promyelocytic leukemia (M3) allowed provided patient has failed prior therapy with both tretinoin and arsenic alone or in combination); Acute lymphoblastic leukemia; Myelodysplastic syndromes; Blastic phase chronic myelogenous leukemia (Failed OR intolerant to imatinib mesylate)
  • Must have failed prior therapy with >= 1 cytotoxic- or biologic-targeted agent (e.g., hypomethylating agents, farnesyl transferase inhibitors, thalidomide, or tyrosine kinase inhibitors); Any number of prior regimens allowed
  • Performance status: ECOG 0-1
  • ALT =< 2.5 times upper limit of normal
  • Bilirubin =< 1.5 mg/dL
  • Creatinine =< 2.0 mg/dL OR Creatinine clearance >= 60 mL/min
  • Fertile patients must use effective contraception
  • No psychiatric illness or social situation that would preclude study compliance
  • Prior bone marrow transplantation allowed
  • At least 2 weeks since prior cytotoxic agents OR at least 5 half-lives for non-cytotoxic agents in the absence of rapidly progressing disease
  • At least 24 hours since prior hydrea for control of peripheral blood leukemia cell counts
  • Hydroxyurea allowed up to 72 hours after start of therapy with sorafenib
  • No persistent, chronic, clinically significant toxicities > grade 1 from prior chemotherapy

Exclusion Criteria:

  • Cytopenias secondary to multilineage bone marrow failure allowed
  • Ineligible for or not willing to undergo allogeneic stem cell transplantation OR no donor available
  • Absolute blast count=< 20,000/mm^3 unless patient has documented fms-like tyrosine kinase 3 internal tandem duplication
  • No evidence of bleeding diathesis (except due to low platelets associated with the primary disease)
  • No New York Heart Association class III or IV congestive heart failure
  • No uncontrolled hypertension (i.e., sustained systolic blood pressure [BP] >= 150 mm Hg or diastolic BP >= 90 mm Hg)
  • No unstable angina pectoris
  • No symptomatic cardiac arrhythmia requiring and not responding to medical intervention
  • Not pregnant or nursing
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to the study drug
  • No swallowing dysfunction that would impede oral ingestion of tablets
  • No active uncontrolled infection
  • No other uncontrolled illness
  • No prior sorafenib
  • No other concurrent investigational or commercial agents, except for standard intrathecal chemotherapy for the treatment of isolated CNS leukemic involvement
  • No other concurrent anticancer agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent therapeutic anticoagulation (Concurrent prophylactic anticoagulation [i.e., low-dose warfarin, catheter flushing with heparin] of venous or arterial access devices allowed)
  • No concurrent cytochrome P450 enzyme-inducing antiepileptic agents, including, but not limited to, any of the following: Phenytoin; Carbamazepine; Phenobarbital; Rifampin
  • No concurrent Hypericum perforatum (St. John's wort)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I
Patients receive oral sorafenib once or twice daily on days 1-5, 8-12, and 15-19.
Drug: Sorafenib Tosylate
Given orally
Other Names:
  • BAY 54-9085
  • Nexavar
  • BAY 43-9006 Tosylate
  • sorafenib
EXPERIMENTAL: Arm II
Patients receive oral sorafenib once or twice daily on days 1-14.
Drug: Sorafenib Tosylate
Given orally
Other Names:
  • BAY 54-9085
  • Nexavar
  • BAY 43-9006 Tosylate
  • sorafenib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: 21 days
21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (ACTUAL)

December 1, 2010

Study Registration Dates

First Submitted

September 20, 2005

First Submitted That Met QC Criteria

September 20, 2005

First Posted (ESTIMATE)

September 22, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

April 28, 2015

Last Update Submitted That Met QC Criteria

April 27, 2015

Last Verified

February 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00081 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • P30CA016672 (U.S. NIH Grant/Contract)
  • U01CA062461 (U.S. NIH Grant/Contract)
  • 6742 (OTHER: CTEP)
  • CDR0000442847
  • 2004-0702 (OTHER: M D Anderson Cancer Center)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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