Completed

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)

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What is being tested

Imatinib Mesylate (Gleevec)

+ PTK 787 (vatalanib)
Drug
Who is being recruted

Bone Marrow Diseases
+11

+ Chronic Disease
+ Hematologic Diseases
Over 15 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: July 2004
See protocol details

Summary

Principal SponsorM.D. Anderson Cancer Center
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: July 1, 2004Actual date on which the first participant was enrolled.

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.

Official TitlePh 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) 
NCT00088231
Principal SponsorM.D. Anderson Cancer Center
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
9 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 15 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Bone Marrow Diseases
Chronic Disease
Hematologic Diseases
Leukemia
Leukemia, Myeloid
Metaplasia
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Disease Attributes
Primary Myelofibrosis
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.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
For 1 week prior to receipt of study combination regimen, all patients will receive single agent PTK 787 at dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Patients should not have a grade 3 or 4 PTK 787-related adverse events in order to begin study combination therapy with a imatinib on day 8. On Day 8, PTK 787 250 mg by mouth every day and imatinib 600 mg by mouth every day (for Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia- blastic phase (CML-BP) and imatinib 400 mg by mouth every day (for Agnogenic Myeloid Metaplasia (AMM). Length of therapy is four courses; each course equals 28 days. Patients assessed for response after each course.

600 mg by mouth every day (for AML, CML-BP) for a 28 day cycle. 400 mg by mouth every day (for AMM) for a 28 day cycle.

For 1 week prior to receipt of the study combination regimen, all patients will receive single agent PTK 787 at the dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Starting dose: 250 mg by mouth every day for a 28 day cycle.
Group II
Experimental
For 1 week prior to receipt of study combination regimen, all patients will receive single agent PTK 787 at dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Patients should not have a grade 3 or 4 PTK 787-related adverse events in order to begin study combination therapy with a imatinib on day 8. PTK 787 250 mg by mouth for Days 1 - 7.

For 1 week prior to receipt of the study combination regimen, all patients will receive single agent PTK 787 at the dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Starting dose: 250 mg by mouth every day for a 28 day cycle.
Study Objectives
Primary Objectives

Time to response is defined as the period of time from the date of first study drug administration until the first objective documentation of response.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
M.D. Anderson Cancer CenterHouston, United StatesSee the location
CompletedOne Study Center