search
Back to results

Oblimersen and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
oblimersen sodium
imatinib mesylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Cancer and Leukemia Group B

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (oblimersen sodium, imatinib mesylate)

Arm Description

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.

Outcomes

Primary Outcome Measures

Cytogenetic response rate in bone marrow

Secondary Outcome Measures

Hematologic response rate in peripheral blood
Cytogenetic response rates
Molecular response rates
Duration of response
Toxicities of concomitant treatment, reported using the NCI Common Toxicity Criteria version 2.0

Full Information

First Posted
November 12, 2002
Last Updated
June 3, 2013
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00049192
Brief Title
Oblimersen and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
November 2002 (undefined)
Primary Completion Date
November 2005 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase Chronic Myelogenous Leukemia, Relapsing Chronic Myelogenous Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (oblimersen sodium, imatinib mesylate)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
oblimersen sodium
Other Intervention Name(s)
augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Other Intervention Name(s)
CGP 57148, Gleevec, Glivec
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Cytogenetic response rate in bone marrow
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Hematologic response rate in peripheral blood
Time Frame
Up to 84 days
Title
Cytogenetic response rates
Time Frame
Up to 84 days
Title
Molecular response rates
Time Frame
Up to 84 days
Title
Duration of response
Time Frame
Up to 5 years
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meir Wetzler
Organizational Affiliation
Cancer and Leukemia Group B
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer and Leukemia Group B
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60606
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Oblimersen and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

We'll reach out to this number within 24 hrs