Oblimersen and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00049192
First received: November 12, 2002
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Chronic Phase Chronic Myelogenous Leukemia
Relapsing Chronic Myelogenous Leukemia
Biological: oblimersen sodium
Drug: imatinib mesylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE II STUDY OF G3139 (GENASENSE™, NSC # 683428 IND # 58842) + IMATINIB MESYLATE (GLEEVEC®, STI571) IN PATIENTS WITH IMATINIB-RESISTANT CHRONIC MYELOID LEUKEMIA

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Cytogenetic response rate in bone marrow [ Time Frame: 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hematologic response rate in peripheral blood [ Time Frame: Up to 84 days ] [ Designated as safety issue: No ]
  • Cytogenetic response rates [ Time Frame: Up to 84 days ] [ Designated as safety issue: No ]
  • Molecular response rates [ Time Frame: Up to 84 days ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Toxicities of concomitant treatment, reported using the NCI Common Toxicity Criteria version 2.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 43
Study Start Date: November 2002
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049192

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Meir Wetzler Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049192     History of Changes
Other Study ID Numbers: NCI-2012-02790, CALGB 10107, U10CA031946
Study First Received: November 12, 2002
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 29, 2014