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


Phase 1
18 Years
N/A
Not Enrolling
Both
Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), 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), Adult Acute Myelomonocytic Leukemia (M4), Adult Acute Promyelocytic Leukemia (M3), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Blastic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes

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Trial Information

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


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.


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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Jorge Cortes

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00081

NCT ID:

NCT00217646

Start Date:

October 2005

Completion Date:

Related Keywords:

  • Adult Acute Basophilic Leukemia
  • Adult Acute Eosinophilic Leukemia
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • 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)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Acute Promyelocytic Leukemia (M3)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Blastic Phase Chronic Myelogenous Leukemia
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes
  • Congenital Abnormalities
  • Blast Crisis
  • Leukemia
  • Leukemia, Basophilic, Acute
  • Leukemia, Eosinophilic, Acute
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Promyelocytic, Acute
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Chronic
  • Hypereosinophilic Syndrome

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030