Ph I/II Study of PTK 787 (Vatalanib) and Gleevec (Imatinib) in Patients With Refractory Acute Myelogenous Leukemia (AML), Agnogenic Myeloid Metaplasia (AMM), and Chronic Myelogenous Leukemia- Blastic Phase (CML-BP)
- Patients with relapsed or refractory AML (including refractory anemia with excess of
blasts [RAEB], refractory anemia with excess of blasts in transition to AML [RAEBT],
or untreated AML when standard chemotherapy is not considered appropriate or is
refused, CML in blastic phase, and agnogenic myeloid metaplasia (AMM)
- Age 15 years or greater (separate pediatric studies will be conducted if results of
adult studies are considered sufficiently positive)
- Laboratory values less than or equal to 2 weeks prior to study entry - Serum
bilirubin 1.5mg/dL, unless considered due to organ leukemic involvement or Gilbert's
syndrome. - SGOT or SGPT less than or equal to 2.5 x upper limit of normal. - Serum
creatinine less than or equal to 2mg/dL,
- Negative for proteinuria based on dip stick reading OR, if documentation of +1 result
for protein on dip stick reading, then total urinary protein less than or equal to
500 mg and measured creatinine clearance (CrCl) greater than or equal to 50 mL/min
from a 24-hour urine collection.
- The effects of PTK 787 and imatinib on the developing human fetus are unknown. For
this reason and because inhibitors of mRNA translation are known to be teratogenic,
women of child-bearing potential and men must agree to use adequate contraception
(barrier method of birth control; abstinence) for the duration of study
- Due to possible interactions with study drugs, oral contraceptives should not be
used. Should a woman become pregnant or suspect she is pregnant while participating
in this study, she should inform her treating physician immediately. If the partner
of a male patient taking PTK 787 and/or Gleevec conceives, the physician should be
- Ability to understand and the willingness to sign a written informed consent
- Performance Status less than or equal to 2.
- Patients who have had cytotoxic chemotherapy, except for hydroxyurea, or radiotherapy
within 7 days prior to entering the study. Patients will have cleared all toxicities
from prior therapies before starting this study combination.
- Patients who have received investigational drugs less than or equal to 2 weeks prior
to study entry
- Prior therapy with anti-VEGF agents.
- Concomitant administration of anticancer drugs is not permitted, except for
hydroxyurea. Leukopheresis is allowed within the first 28 days of treatment if
required to control elevated blast levels or platelet counts. Within the first 28
days of treatment, hydroxyurea may be given at a maximum dose of 5 g daily for up to
a total of 7 days. For leukopheresis, a maximum of 2 procedures per week or 4
procedures during the first 28 days is allowed.
- Patients may not be receiving any other cytotoxic investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to PTK 787 or imatinib.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled
diabetes, interstitial pneumonia or extensive and symptomatic interstitial fibrosis
of the lung, chronic liver disease or psychiatric illness/social situations that
would limit compliance with study requirements.
- Uncontrolled intercurrent illness including, not limited to, ongoing uncontrolled
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled high blood pressure, history of labile hypertension, history
of poor compliance with an antihypertensive regimen, myocardial infarction less than
or equal to 6 months prior to registration, uncontrolled diabetes, interstitial
pneumonia or extensive and symptomatic interstitial fibrosis of lung, chronic liver
disease or psychiatric illness/social situations that limits compliance with study
- Pleural effusion or ascites that causes respiratory compromise (greater than or equal
to Common Toxicity Criteria (CTC) grade 2 dyspnea).
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of PTK787 (i.e., ulcerative disease, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to
swallow the tablets).
- Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are
excluded - A separate study for patients with HIV will be performed if indicated.
- Pregnant women are excluded from this study because PTK 787 and imatinib may have a
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 PTK 787 or imatinib, breastfeeding patients will not be eligible.
- Patients with known central nervous system (CNS) disease are excluded.
- Patients with a history of another primary malignancy less than or equal to 5 years,
with the exception of inactive basal or squamous cell carcinoma of the skin.
- Patients w/ recent major surgery are excluded (less than 4 wks of starting this
study) or minor surgery less than or equal to 2 weeks prior to randomization.
Insertion of a vascular access device is not considered major or minor surgery in
this regard. Patients must have recovered from all surgery-related toxicities.
- Patients who are taking warfarin sodium (Coumadin) or similar oral anticoagulants
that are metabolized by the cytochrome P450 system. Heparin is allowed.