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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00217646

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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 Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Dec 1, 2010

Arms and Interventions

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 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib
Experimental: Arm II Patients receive oral sorafenib once or twice daily on days 1-14.	Drug: Sorafenib Tosylate Given orally Other Names: BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib

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 43-9006 Tosylate

BAY 54-9085

Nexavar

sorafenib

Experimental: Arm II

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

Drug: Sorafenib Tosylate

Given orally

Other Names:

BAY 43-9006 Tosylate

BAY 54-9085

Nexavar

sorafenib

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [21 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)