Oblimersen and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

NCT ID: NCT00049192

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-11-30

Brief Summary

Phase II trial to study the effectiveness of combining oblimersen with imatinib mesylate in treating patients who have chronic myelogenous leukemia that has not responded to previous treatment with imatinib mesylate. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Oblimersen may help imatinib mesylate kill more cancer cells by making cancer cells more sensitive to the drug.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the cytogenetic response rate of patients with CML who have had less than a complete hematologic response or less than major cytogenetic response to imatinib mesylate and who have been treated after two cycles of imatinib mesylate + G3139.

SECONDARY OBJECTIVES:

I. To estimate the hematologic, cytogenetic and molecular response rate and duration in patients diagnosed with CML who have been treated after two and four cycles of imatinib mesylate + G3139.

II. To estimate the toxicity of these two drugs given in combination in a cooperative group setting.

OUTLINE:

Patients receive oblimersen IV continuously on days 1-10 and oral imatinib mesylate once or twice daily. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without a hematologic response after 2 courses go off study. Patients with complete or partial response after 4 courses may continue to receive oral imatinib mesylate daily.

Patients in cohort 2 receive an escalated dose of oblimersen; if well tolerated, subsequent cohorts receive oblimersen at the higher dose with the original dose of imatinib mesylate. If oblimersen is not well tolerated in cohort 2, subsequent cohorts receive the original dose of oblimersen with an escalated dose of imatinib mesylate. The first 6 patients accrued continue to receive the original dose (dose taken prior to study) of imatinib mesylate throughout the study.

Patients are followed monthly for 3 months and then every 3 months for 5 years.

Conditions

Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (oblimersen sodium, imatinib mesylate)

Patients receive oblimersen IV continuously on days 1-10 and oral imatinib mesylate once or twice daily. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without a hematologic response after 2 courses go off study. Patients with complete or partial response after 4 courses may continue to receive oral imatinib mesylate daily.

Patients in cohort 2 receive an escalated dose of oblimersen; if well tolerated, subsequent cohorts receive oblimersen at the higher dose with the original dose of imatinib mesylate. If oblimersen is not well tolerated in cohort 2, subsequent cohorts receive the original dose of oblimersen with an escalated dose of imatinib mesylate. The first 6 patients accrued continue to receive the original dose (dose taken prior to study) of imatinib mesylate throughout the study.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

imatinib mesylate

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

imatinib mesylate

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; CGP 57148; Gleevec; Glivec

Eligibility Criteria

Inclusion Criteria

• Diagnosis of chronic myeloid leukemia (CML) in chronic phase; clonal cytogenetic evolution alone does not exclude patients
• Patients in whom a Philadelphia chromosome [t(9;22)] or a variant translocation is not detectable by cytogenetic studies are eligible if they meet one of the following criteria:

• Polymerase chain reaction (PCR) positive fusion transcripts for BCR/ABL;
• BCR/ABL translocation present by fluorescence in situ hybridization (FISH)
• Patients must have received prior therapy with imatinib mesylate (>= 400 mg/day for > 8 weeks without a complete hematologic response or >= 400 mg/day for > 6 months without a major cytogenetic response) and must not have evidence of progressive disease (accelerated or blast phases)
• Patients must have received a stable dose of imatinib mesylate >= 600 mg/day for at least 4 weeks without > grade 1 toxicities; the first six patients enrolled will be restricted to receiving an imatinib mesylate dose of 600 mg/day while on study
• No prior therapy with hydroxyurea, cytarabine, interferon, anagrelide, homoharringtonine, or any other investigational agent within 4 weeks of study enrollment
• Patients may not have received other antineoplastic medications (e.g., busulfan)
• No prior stem cell transplantation
• Patients must not require oral anticoagulant therapy
• Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control throughout the duration of protocol treatment and for at least three months after the last dose of imatinib mesylate
• No other serious illnesses which would limit survival to < 2 years, or a psychiatric condition which would prevent compliance with treatment or informed consent
• No uncontrolled cardiovascular disease, diabetes, pulmonary disease, or infection, which in the opinion of the treating physician, would make this protocol treatment unreasonably hazardous for the patient
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year
• Bilirubin =< 2 mg/dL
• Creatinine =< 2 mg/dL
• AST =< 1.5 x Upper Limit of Normal
• PTT =< 1.5 x Upper limit of Normal
• BHCG Negative (if patient of childbearing potential)

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Meir Wetzler

Role: PRINCIPAL_INVESTIGATOR

Cancer and Leukemia Group B

Locations

Cancer and Leukemia Group B

Chicago, Illinois, United States

Countries

United States

Other Identifiers

CALGB 10107

Identifier Type: -

Identifier Source: secondary_id

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02790

Identifier Type: -

Identifier Source: org_study_id