Study of Lonafarnib and Gleevec in Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00047502
First received: October 8, 2002
Last updated: February 20, 2012
Last verified: February 2012
  Purpose

The purpose of this study if to investigate the effect of lonafarnib (SCH66336) in combination with Gleevec in the treatment of CML.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Drug: Lonafarnib (SCH66336)
Drug: Imatinib Mesylate (Gleevec)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Lonafarnib (SCH66336) and Gleevec (Imatinib Mesylate) in Chronic Myelogenous Leukemia (CML)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Dose-Limiting Toxicity (DLT) defined as grade 3 or 4 non-hematologic toxicity (NCI common criteria, version 2.0). Grade 3 or 4 nausea and vomiting considered DLT only if uncontrolled by antiemetics. Grade 3 or 4 diarrhea considered DLT only if uncontrolled for 48 hours despite adequate antidiarrheal therapy.


Enrollment: 23
Study Start Date: November 2002
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gleevec + SCH 66336

Participants in CHRONIC PHASE receive Gleevec 400 mg by mouth every day, and SCH66336 100 mg by mouth twice a day.

Participants in ACCELERATED OR BLASTIC PHASE receive Gleevec 600 mg by mouth every day, and SCH66336 100 mg by mouth twice a day.

Drug: Lonafarnib (SCH66336)

Participants in CHRONIC PHASE receive Gleevec 400 mg by mouth every day, and SCH66336 100 mg by mouth twice a day.

Participants in ACCELERATED OR BLASTIC PHASE receive SCH66336 100 mg by mouth twice a day.

Participants in ACCELERATED OR BLASTIC PHASE receive SCH66336 100 mg by mouth twice a day.

Other Names:
  • SCH66336
  • Sarasar
Drug: Imatinib Mesylate (Gleevec)

Participants in CHRONIC PHASE receive Gleevec 400 mg by mouth every day.

Participants in ACCELERATED OR BLASTIC PHASE receive Gleevec 600 mg by mouth every day.

Other Names:
  • Gleevec
  • Imatinib
  • ST1571
  • NSC-716051

Detailed Description:

Existing pre-clinical and clinical data suggest that SCH66336, a farnesyl transferase inhibitor,exhibits significant activity against CML cells, and in fact may have synergistic activity in combination with imatinib mesylate. Thus, the objectives to the study are (1) to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of lonafarnib (SCH66336), a farnesyl transferase inhibitor, in combination with imatinib mesylate (Gleevec) in patients with chronic phase, accelerated phase, and blast crisis CML; (2) to assess the pharmacokinetics of the combination of lonafarnib and Gleevec in these patients; and (3) to assess in a preliminary way the biologic activity of the combination of lonafarnib and Gleevec in these patients.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Patients with Philadelphia chromosome (ph) positive CML in any of the following categories:

    1. Chronic phase patients must have failed therapy with Gleevec. Failure will be defined as: (i) Patients who have not achieved or have lost their hematologic response at 3 months from the start of therapy with Gleevec, or (ii) Patients who have not achieved or have lost their cytogenetic response after 6 months of therapy with Gleevec, or (iii) Patients who have not achieved or have lost their major cytogenetic response after 12 months of therapy with Gleevec.
    2. Patients in accelerated phase, defined as the presence of any of the following features: (i) blasts in peripheral blood (PB) or bone marrow (BM) >/= 15% (but < 30%), (ii) blasts + promyelocytes in PB or BM >/= 30%, (iii) basophils in PB or BM >/= 20%, (iv) platelets < 100 x 10e9/L unrelated to therapy, (v) clonal evolution.
    3. Patients in blast phase, defined by the presence of >/= 30% blasts in peripheral blood and/or bone marrow, or the presence of extramedullary disease.

      2) Patients in accelerated or blastic phase are eligible whether they have received and/or failed Gleevec or not.

      3) Age >/= 16 years.

      4) Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping eith the policies of the hospital. The only acceptable consent form is attached at the end of the protocol.

      5) Performance status </= 2 by Zubrod scale.

      6) Patients must have adequate hepatic functions (bilirubin </= 2.0 mg/dl) and renal functions (creatinine </= 2 mg/dl).

      7) Exclusion criteria:

    1. Patients with QTc > 500 msec.
    2. Patients with severe heart disease (cardiac class III and IV) will be excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00047502

Locations
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Jorge E. Cortes, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00047502     History of Changes
Other Study ID Numbers: ID02-221
Study First Received: October 8, 2002
Last Updated: February 20, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 23, 2014