Oblimersen and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

NCT00049192 | Completed Phase 2

• 3 other identifiers: NCI-2012-02790CALGB 10107U10CA031946
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Cytogenetic response rate in bone marrow

  42 days

Secondary Outcomes (5)

• Hematologic response rate in peripheral blood

  Up to 84 days

• Cytogenetic response rates

  Up to 84 days

• Molecular response rates

  Up to 84 days

• Duration of response

  Up to 5 years

• Toxicities of concomitant treatment, reported using the NCI Common Toxicity Criteria version 2.0

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (oblimersen sodium, imatinib mesylate)

EXPERIMENTAL

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; Drug: imatinib mesylate; Other: laboratory biomarker analysis

Interventions

oblimersen sodium BIOLOGICAL

Given IV

Also known as: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

Treatment (oblimersen sodium, imatinib mesylate)

imatinib mesylate DRUG

Given PO

Also known as: CGP 57148, Gleevec, Glivec

Treatment (oblimersen sodium, imatinib mesylate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (oblimersen sodium, imatinib mesylate)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Cancer and Leukemia Group B

Chicago, Illinois, 60606, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase

Interventions

oblimersen; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Meir Wetzler

  Cancer and Leukemia Group B

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2002
• First Posted: January 27, 2003
• Study Start: November 1, 2002
• Primary Completion: November 1, 2005
• Last Updated: June 4, 2013

Record last verified: 2013-06

Locations

US (1)