Zarnestra and Gleevec in Chronic Phase Chronic Myelogenous Leukemia - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00040105

Purpose

The goal of this clinical research study is to find the highest safe dose of the drugs ZarnestraTM (R115777) and Gleevec (imatinib mesylate) that can be given in combination for the treatment of chronic myelogenous leukemia (CML) in chronic phase. The effect of this combination on the leukemia will also be studied.

Optional Procedures: Participants will be asked to give a small additional amount of blood and bone marrow whenever blood or bone marrow is already being drawn for routine testing. The purpose of this is to investigate the effect of this therapy on the leukemia cells and understand better how the study drugs work together.

Participants will also be asked to have some extra bone marrow samples collected. These samples will be used to analyze RNA. Thousands of different genes will be looked at to see if any of these are affecting the way R115777 works.

Condition	Intervention	Phase
Leukemia, Myeloid, Chronic	Drug: R115777 (Zarnestra) Drug: Imatinib mesylate (Gleevec)	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Imatinib R 115777 Tipifarnib Imatinib mesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I Study of Zarnestra (R115777.USA30) and Gleevec (Imatinib Mesylate) in Chronic Phase Chronic Myelogenous Leukemia (CML)

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To determine the maximum tolerated doses (MTD) of ZARNESTRA (R115777), a farnesyl transferase inhibitor (FTI), and Gleevec, when given in combination to patients with chronic phase CML. [ Time Frame: July 2006 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the toxicity of the ZARNESTRA and Gleevec combination in these patients. [ Time Frame: July 2009 ] [ Designated as safety issue: No ]

Enrollment:	26
Study Start Date:	October 2002
Study Completion Date:	March 2009
Primary Completion Date:	July 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Zarnestra (R115777)+ Gleevec (Imatinib Mesylate)	Drug: R115777 (Zarnestra) R115777 (400 mg PO Two Times a Day) Drug: Imatinib mesylate (Gleevec) Gleevec (400 mg PO Four Times a Day)

Detailed Description:

R115777 is a new drug that blocks the function of an enzyme that is important in making some proteins work. One of the most important targets for this enzyme is a protein that can make cells become cancer. Imatinib mesylate is a drug that blocks the function of the protein that comes from the Philadelphia chromosome. The Philadelphia chromosome is an abnormality in chromosomes 9 and 22 that changes blood cells into leukemia cells.

Before treatment starts, participants will have a physical exam, blood tests (About 3 tubes, 2 teaspoons each), and a bone marrow biopsy. The bone marrow will be removed with a large needle.

Participants in this study will take imatinib mesylate by mouth every day for as long as they stay on study, which means as long as it works.

Participants will also take R115777 twice a day for 2 weeks. This will be repeated every 3 weeks. The amount of each of these medications that participants take will depend on when they enter the study. The doses will be slowly increased from participant to participant until the highest dose that does not cause serious side effects is found.

Participants will be asked to visit their doctor for a physical exam and measurement of vital signs. The frequency of doctor visits will vary depending on physical condition. Blood tests (about 2 teaspoons each) will be done every week during the first 3 weeks of treatment. Blood tests will then be done every 8-12 weeks for the length of the study, as needed. The blood samples will be used for routine lab tests. A bone marrow sample will also be taken to check and measure cells related to the disease every 3 months in the first year and then every 6-12 months. Participants can stay on study for as long as the treatment is considered to be beneficial. Participants will be taken off study if their disease gets worse or intolerable side effects occur.

This is an investigational study. The FDA has authorized the use of imatinib mesylate for patients with CML. It is the combination of imatinib mesylate and R115777 that is experimental. R115777 has been authorized for investigational use only. A maximum of 30 patients will take part in this study. All will be enrolled at M. D. Anderson.

Optional Procedures: Participants who agree will have an additional small amount of bone marrow (about 1 teaspoon) every time they have a bone marrow aspiration. This does not require any additional bone marrow aspiration procedures. A small amount of blood (about 1 teaspoon) will also be collected periodically when scheduled blood samples are collected for routine tests.

Participants who agree will also have two bone marrow aspirates (about 1 teaspoon, total) collected at the start of the study and at the end of Cycle 2.

The RNA sample that is taken from the aspirates will not be stored. Participants who change their mind after giving bone marrow for this study may ask for the samples to be destroyed.

You do not have to agree to take part in the optional procedures in order to receive treatment on this study.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients 16 years or older with Philadelphia chromosome (Ph)- or BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR) are eligible if they are not candidates for known regimens or protocol treatments of higher efficacy or priority. Patients must be in the chronic phase of CML.
Patients must have failed therapy with imatinib mesylate. Failure will be defined as: 1) patients who have failed to achieve or have lost a complete hematologic remission at 3 months from the start of therapy with imatinib mesylate, or 2) patients who have failed to achieve or have lost at least a minimal cytogenetic response after 6 months of therapy with imatinib mesylate, or 3) patients who have failed to achieve or have lost a major cytogenetic response after 12 months of therapy with imatinib mesylate
Chronic phase will be defined by the following features: 1) blasts in peripheral blood or bone marrow <10%, 2) basophils in PB or BM <20%, 3) platelets >100 x 10(9)/L, 4) absence of clonal evolution
Patients must sign an informed consent
Performance status </= 2 by Zubrod scale
Patients must have adequate hepatic functions (bilirubin </= 2.0 mg/dl) and renal functions (creatinine </=2 mg/dl)
WBC </= 30 x 10(9)/L. Patients may receive Hydroxyurea (or other similar agent) to bring the WBC below this level. Hydroxyurea (or its equivalent) must be discontinued 24 hours before the start of therapy.
Patients of childbearing potential should practice effective methods of contraception.

Exclusion Criteria:

Patients under 16 years of age.
Pregnant and nursing females will be excluded.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00040105

Locations

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

Sponsors and Collaborators

M.D. Anderson Cancer Center

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

Principal Investigator:

Jorge E Cortes, MD

U.T.M.D. Anderson Cancer Center

More Information

Additional Information:

M.D. Anderson's Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	The University of Texas M. D. Anderson Cancer Center ( Jorge Cortes M.D./Professor )
Study ID Numbers:	ID02-169
Study First Received:	June 19, 2002
Last Updated:	March 20, 2009
ClinicalTrials.gov Identifier:	NCT00040105 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Chronic Myelogenous Leukemia, Chronic Phase
R115777
Zarnestra
Tipifarnib
Imatinib Mesylate

Gleevec
Imatinib
STI571
NSC-716051

Study placed in the following topic categories:

Imatinib
Leukemia
Hematologic Diseases
Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Myelogenous Leukemia

Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid
Bone Marrow Diseases
Protein Kinase Inhibitors
Tipifarnib

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hematologic Diseases
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Protein Kinase Inhibitors

Pharmacologic Actions
Imatinib
Leukemia
Neoplasms
Therapeutic Uses
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases
Tipifarnib

ClinicalTrials.gov processed this record on May 07, 2009