ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00217646
Recruitment Status : Completed
First Posted : September 22, 2005
Last Update Posted : April 28, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

September 20, 2005
September 22, 2005
April 28, 2015
October 2005
December 2010   (Final data collection date for primary outcome measure)
Maximum tolerated dose (MTD) assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 21 days ]
Not Provided
Complete list of historical versions of study NCT00217646 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia
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.

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.

Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adult Acute Basophilic Leukemia
  • Adult Acute Eosinophilic Leukemia
  • Adult Acute Megakaryoblastic Leukemia
  • Adult Acute Monoblastic Leukemia
  • Adult Acute Monocytic Leukemia
  • Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
  • Adult Acute Myeloid Leukemia With Maturation
  • Adult Acute Myeloid Leukemia With Minimal Differentiation
  • Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1
  • Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL
  • Adult Acute Myeloid Leukemia Without Maturation
  • Adult Acute Myelomonocytic Leukemia
  • Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA
  • Adult Erythroleukemia
  • Adult Pure Erythroid Leukemia
  • Alkylating Agent-Related Acute Myeloid Leukemia
  • Blastic Phase
  • de Novo Myelodysplastic Syndrome
  • Previously Treated Myelodysplastic Syndrome
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndrome
Drug: Sorafenib Tosylate
Given orally
Other Names:
  • BAY 43-9006 Tosylate
  • BAY 54-9085
  • Nexavar
  • sorafenib
  • Experimental: Arm I
    Patients receive oral sorafenib once or twice daily on days 1-5, 8-12, and 15-19.
    Intervention: Drug: Sorafenib Tosylate
  • Experimental: Arm II
    Patients receive oral sorafenib once or twice daily on days 1-14.
    Intervention: Drug: Sorafenib Tosylate
Borthakur G, Kantarjian H, Ravandi F, Zhang W, Konopleva M, Wright JJ, Faderl S, Verstovsek S, Mathews S, Andreeff M, Cortes JE. Phase I study of sorafenib in patients with refractory or relapsed acute leukemias. Haematologica. 2011 Jan;96(1):62-8. doi: 10.3324/haematol.2010.030452. Epub 2010 Oct 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
Not Provided
Not Provided
December 2010   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00217646
NCI-2009-00081
NCI-2009-00081 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000442847
2004-0702 ( Other Identifier: M D Anderson Cancer Center )
6742 ( Other Identifier: CTEP )
P30CA016672 ( U.S. NIH Grant/Contract )
U01CA062461 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Jorge Cortes M.D. Anderson Cancer Center
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP