Zarnestra and Gleevec in Chronic Phase Chronic Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00040105
Recruitment Status : Completed
First Posted : June 21, 2002
Last Update Posted : August 1, 2012
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Chronic Drug: Zarnestra (R115777) Drug: Gleevec (Imatinib mesylate) Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Zarnestra (R115777.USA30) and Gleevec (Imatinib Mesylate) in Chronic Phase Chronic Myelogenous Leukemia (CML)
Study Start Date : October 2002
Actual Primary Completion Date : March 2009
Actual Study Completion Date : March 2009

Arm Intervention/treatment
Experimental: Zarnestra + Gleevec Drug: Zarnestra (R115777)

Starting Dose:

300 mg by mouth (PO) Twice daily

Other Name: Tipifarnib

Drug: Gleevec (Imatinib mesylate)

Starting Dose:

300 mg By Mouth (PO) daily

Other Names:
  • Imatinib
  • STI571
  • NSC-716051

Primary Outcome Measures :
  1. Maximum tolerated doses (MTD) [ Time Frame: Every 3 months ]

Secondary Outcome Measures :
  1. Toxicity of the ZARNESTRA and Gleevec combination [ Time Frame: July 2009 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00040105

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.
Principal Investigator: Jorge E Cortes, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00040105     History of Changes
Other Study ID Numbers: ID02-169
First Posted: June 21, 2002    Key Record Dates
Last Update Posted: August 1, 2012
Last Verified: July 2012

Keywords provided by M.D. Anderson Cancer Center:
Chronic Myelogenous Leukemia, Chronic Phase
Imatinib Mesylate

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action