Study of Lonafarnib and Gleevec in Chronic Myelogenous Leukemia

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00047502

Collaborator

(none)

Enrollment

Location

Arm

41.3

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of Lonafarnib (SCH66336) and Gleevec (Imatinib Mesylate) in Chronic Myelogenous Leukemia (CML)

Actual Study Start Date :

Nov 1, 2002

Actual Primary Completion Date :

Apr 10, 2006

Actual Study Completion Date :

Apr 10, 2006

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity (DLT) [3 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Patients with Philadelphia chromosome (ph) positive CML in any of the following categories:
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.
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.
Patients in blast phase, defined by the presence of >/= 30% blasts in peripheral blood and/or bone marrow, or the presence of extramedullary disease.

Patients in accelerated or blastic phase are eligible whether they have received and/or failed Gleevec or not.
Age >/= 16 years.
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.
Performance status </= 2 by Zubrod scale.
Patients must have adequate hepatic functions (bilirubin </= 2.0 mg/dl) and renal functions (creatinine </= 2 mg/dl).
Exclusion criteria: