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PTK 787 and Gleevec in Patients With AML, AMM, and CML-BP

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Myelogenous Leukemia; Agnogenic Myeloid Metaplasia; Chronic Myelogenous Leukemia

Intervention: Imatinib Mesylate (Gleevec) (Drug); PTK 787 (vatalanib) (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: M.D. Anderson Cancer Center

Summary

The goal of this clinical research study is to find the highest safe doses of PTK 787 (vatalanib) and Gleevec (imatinib mesylate) that can be given to treat Chronic Myelogenous Leukemia-Blastic Phase (CML-BP), Refractory Acute Myelogenous Leukemia (AML), or Agnogenic Myeloid Metaplasia (AMM). Another goal is to see how effective this combination treatment is.

Clinical Details

Official title: 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)

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

Primary outcome: Time to Response

Detailed description: Rationale: The purpose of this study is to combine PTK-787, a potent orally vascular endothelial growth factor (VEGF) receptor inhibitor (in disorders where VEGF is known to be involved in the pathophysiology), with Imatinib mesylate (IM), a protein-tyrosine kinase inhibitor of abl, Bcr-Abl, platelet derived growth factor (PDGF), and c-Kit (in same disorders where these kinases are believed to be important). The potential synergy between oral agents that inhibit these kinases in disorders where each of the two agents have some, but inadequate, single agent activity is being studied in this protocol. We will also have an opportunity to assess if there is any correlation between response and individual kinase mutations e. g., c-Kit in patients with AML. If improved outcomes are observed, further studies will be indicated to investigate which, if either, agent is predominantly

responsible for such a benefit - these studies will be facilitated by the availability of

more potent e. g., (AMN107 as an abl inhibitor), (Bevacizumab, AG013736 as VEGF inhibitors) agents which will help to define the relative importance of the various inhibitory activities. Objectives: To determine the maximum tolerated doses (MTD) and pharmacokinetics (PK) of PTK 787 and imatinib mesylate, when given in combination to patients with refractory acute myelogenous leukemia (AML), agnogenic myeloid metaplasia (AMM) and chronic myelogenous leukemia in blastic phase (CML-BP). To determine the efficacy (response rate, survival, time to progression, time to treatment failure, duration of response) of the MTD in these study populations.

Eligibility

Minimum age: 15 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 participation.

- 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 notified

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

document.

- Performance Status less than or equal to 2.

Exclusion Criteria:

- 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 requirements.

- 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.

Locations and Contacts

M.D. Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information

M.D. Anderson Cancer Center's website

Starting date: July 2004
Last updated: January 19, 2012

Page last updated: August 23, 2015

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