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A Phase II Study of Sunitinib Malate in Idiopathic Myelofibrosis

Phase 2
18 Years
Not Enrolling
Accelerated Phase Chronic Myelogenous Leukemia, Acute Undifferentiated Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, 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), Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Blastic Phase Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, Mast Cell Leukemia, Meningeal Chronic Myelogenous Leukemia, Primary Myelofibrosis, Progressive Hairy Cell Leukemia, Initial Treatment, Prolymphocytic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia, T-cell Large Granular Lymphocyte Leukemia, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Adult Acute Myeloid Leukemia, Untreated Hairy Cell Leukemia

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Trial Information

A Phase II Study of Sunitinib Malate in Idiopathic Myelofibrosis


I. Assess the response rate and the duration of response in patients with idiopathic
myelofibrosis treated with sunitinib malate.


I. Assess the safety of sunitinib malate in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral sunitinib malate once daily for 6 weeks. Treatment repeats every 6
weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks.


- At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C)

- At least 4 weeks since prior major surgery

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including azole
antifungals (ketoconazole and itraconazole), clarithromycin, erythromycin, diltiazem,
verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,
nelfinavir), and delavirdine

- At least 12 days since prior and no concurrent CYP3A4 inducers, including rifampin,
rifabutin, carbamazepine, phenobarbital, phenytoin, Hypericum perforatum (St. John's
wort), efavirenz, and tipranavir

- No prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171,
vatalanib, VEGF Trap)

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g.,
warfarin) (Warfarin =< 2 mg/day for prophylaxis of thrombosis and low molecular
weight heparin allowed provided INR =< 1.5)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine,
procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone,
indapamide, and flecainide)

Inclusion Criteria:

- Diagnosis of MF (histologically confirmed) requiring therapy, including those
previously treated and relapsed or refractory (no more than one prior standard acute
leukemia-type chemotherapy regimen; no limit on prior MF - directed therapies) or if
newly diagnosed, with intermediate or high risk according to Lille scoring system
(adverse prognostic factors are: Hb < 10 g/dl, WBC < 4 or > 30 x 10^9/L; risk group:
0 = low, 1 = intermediate, 2 = high), or with symptomatic organomegaly.

- Serum bilirubin levels acceptable if these can be attributed to active hemolysis or MF

- Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels

- Serum creatinine levels
- Eighteen years of age or older.

- ECOG performance status 0-1 (Karnofsky
- Patients must have QTc < 500 msec

- Women of childbearing potential and men must agree to use adequate contraception
(e.g. hormonal or barrier method of birth control; abstinence) for the duration of
study participation. All women of childbearing potential must have a negative
pregnancy test prior to receiving sunitinib. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.

- Ability to understand and the willingness to sign a written informed consent document

- Both men and women and members of all races and ethnic groups are eligible for this

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to beginning treatment or those who have not
recovered from treatment-limiting adverse events (to grade 1 or better) due to agents
administered more than 4 weeks earlier. At least 4 weeks must have elapsed since any
major surgery prior to study enrollment. Continuous use of supportive care
medications (i. e. growth factors, anagrelide, or hydroxyurea) is allowed.

- Patients may not be receiving any other investigational agents.

- Patients who have received prior treatment with any other specific antiangiogenic
agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, VEGF Trap, etc.)
targeting VEGF/VEGFR system. Other agents that may have some antiangiogenic effects
are allowed). (i.e. thalidomide)

- Patients with abnormal QTc prolongation (defined as a QTc interval equal to or
greater than 500 msec) or patients who have a history of serious ventricular
arrhythmia (VT or VF>/= 3 beats in a row or other significant (as judged by treating
physician) ECG abnormalities.Patients with consistently poorly controlled (during the
month prior to study screening) hypertension (systolic blood pressure of 140 mmHg or
higher or diastolic blood pressure of 90 mmHg or higher) despite appropriate medical
management of the hypertension.

- Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
such as warfarin. Exceptions include: patients using warfarin of up to 2 mg daily for
prophylaxis of thrombosis, and patients using low molecular weight heparin provided
the patient's INR is
- Patients with any condition (e.g., gastrointestinal tract disease resulting in an
inability to take oral medication or a requirement for IV alimentation, prior
surgical procedures affecting absorption, or active peptic ulcer disease) that
impairs their ability to swallow and retain sunitinib tablets.

- Patients with any of the following conditions:·Serious or non-healing wound, ulcer,
or bone fracture, history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 28 days of treatment,·cerebrovascular accident (CVA)
or transient ischemic attack, myocardial infarction, cardiac arrhythmia,
stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral
artery bypass graft or stenting, or pulmonary embolism within 12 months prior to
study,·Class III or IV heart failure as defined by the NYHA functional classification

- Because sunitinib is metabolized primarily by the CYP3A4 liver enzyme, the
eligibility of patients taking medications that are potent inducers or inhibitors of
that enzyme will be determined following a review of their case by the Principal
Investigator. Every effort should be made to switch patients taking such agents or
substances to other medications.

- Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid
function in the normal range with medications.

- Patients with uncontrolled intercurrent illness (as judged by treating physician)
including, but not limited to, ongoing or active infections requiring IV antibiotics.

- Pregnant women are excluded from this study because sunitinib is an antiangiogenic
agent with the potential for teratogenic or abortifacient effects. Because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with sunitinib, breastfeeding should be discontinued if the
mother is treated with sunitinib malate.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with sunitinib. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Objective Clinical Response to Sunitinib Therapy

Outcome Description:

Participant response assessed after two cycles of therapy according to categories: 1) complete response, 2) partial response, 3) clinical improvement, 4) stable disease 5) progressive disease, 6) early death from malignant disease, 7) early death from toxicity, 8) early death because of other cause, or 9) unknown (not assessable, insufficient data).

Outcome Time Frame:

After two 6-week treatment courses (12 weeks)

Safety Issue:


Principal Investigator

Srdan Verstovsek

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2006

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Acute Undifferentiated Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • 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)
  • Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
  • Blastic Phase Chronic Myelogenous Leukemia
  • Chronic Myelomonocytic Leukemia
  • Chronic Phase Chronic Myelogenous Leukemia
  • Mast Cell Leukemia
  • Meningeal Chronic Myelogenous Leukemia
  • Primary Myelofibrosis
  • Progressive Hairy Cell Leukemia, Initial Treatment
  • Prolymphocytic Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Acute Myeloid Leukemia
  • Stage I Chronic Lymphocytic Leukemia
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage IV Chronic Lymphocytic Leukemia
  • T-cell Large Granular Lymphocyte Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Untreated Hairy Cell Leukemia
  • Congenital Abnormalities
  • Primary Myelofibrosis
  • Blast Crisis
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Mast-Cell
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Prolymphocytic
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  • Leukemia, Large Granular Lymphocytic



M D Anderson Cancer Center Houston, Texas  77030