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Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)

This study has been terminated.
(Poor enrollment)
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( ChemGenex Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00114959
First received: June 20, 2005
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

This will be an open label, multi-center study of up to 77 patients with CML in chronic, accelerated or blast phase who have developed resistance to or have failed previous treatment with Gleevec (imatinib mesylate). Because these patients may still be sensitive to Gleevec, adding Homoharringtonine may restore a response to Gleevec or the combined treatment may promote a better response than using Gleevec alone.


Condition Intervention Phase
Myeloid Leukemia, Chronic
Myeloid Leukemia, Chronic, Accelerated-Phase
Blast Phase
Myeloid Leukemia, Chronic, Chronic-Phase
Drug: Homoharringtonine
Drug: Imatinib Mesylate
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 Open-Label Study of the Intravenous Administration of Homoharringtonine (CGX-635) Combined With the Oral Administration of Gleevec in the Treatment of Patients With Chronic Myeloid Leukemia (CML) in Chronic, Accelerated, and Blast Phase

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Proportion of patients with accelerated or blast phase CML who convert to at least chronic phase CML [ Time Frame: Monthly evaluations ] [ Designated as safety issue: No ]
  • Tolerance and toxicity of the combined HHT- imatinib mesylate treatment regimen. [ Time Frame: On going ] [ Designated as safety issue: No ]
  • Proportion of patients with chronic phase CML who are in hematologic remission (CHR) or improved cytogentics at study onset [ Time Frame: Monthly evaluations ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: October 2005
Study Completion Date: March 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Homoharringtonine + Imatinib Mesylate
Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Drug: Homoharringtonine

Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous (IV) infusion daily on Days 1-5 of each 4 week treatment cycle. Participants who do not achieve a meaningful hematologic or cytogenetic response by the end of the fourth cycle are discontinued from the study. Otherwise, participants may continue additional cycles of this combined treatment for a maximum of 12 cycles.

Participants who achieved a molecular or cytogenetic response, or a complete hematologic remission (CHR), could undergo subsequent cycles with a maintenance schedule of homoharringtonine 2.5 mg/m^2 by continuous 24-hour IV infusion daily for 2 days every 4 weeks. Dose escalations in subsequent cycles were allowed by one day at a time if the participant was unable to maintain CHR in the maintenance schedule.

Other Names:
  • Omacetaxine mepesuccinate
  • CGX-635
Drug: Imatinib Mesylate
Taken by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML. For the first cycle of therapy only, imatinib was started on Day 4 of homoharringtonine treatment.
Other Name: Gleevac

Detailed Description:

Every 4 weeks, the study medicine Homoharringtonine will be given by vein daily for 5 days along with continuing daily doses of the approved medicine Gleevec taken by mouth. The safety and effectiveness of this combined treatment in CML patients will be studied. Patients who do not achieve a meaningful hematologic or cytogenetic response after 4 cycles or less will be discontinued. Otherwise, patients may continue additional cycles of this combined treatment for a maximum of 12 cycles.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients 16 years or older
  • Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) in either chronic, accelerated or blast phase
  • Patients with chronic phase CML will be either refractory (failed to achieve hematologic or cytogenetic response) or resistant (responded initially but subsequently lost hematologic or cytogenetic response) to prior imatinib mesylate therapy. Failure to achieve cytogenetic response is defined as follows: no cytogenetic response after 3 months of therapy with imatinib mesylate, no major cytogenetic response at 12 months of therapy, loss of complete cytogenetic response documented twice, or loss of major cytogenetic response at least once.
  • Patients with accelerated or blast phase may be newly diagnosed and previously untreated or if previously treated with imatinib mesylate, will be refractory or resistant to this agent or have failed to achieve at least a complete hematologic or cytogenetic response to treatment, as previously defined.
  • Patients in accelerated phase will meet one or more of the following criteria: greater than or equal to 15% through less than 30% blasts in peripheral blood or bone marrow, greater than or equal to 30% blasts + promyelocytes in peripheral blood or bone marrow, greater than or equal to 20% basophils in peripheral blood, platelet count less than 100*10^9/L unrelated to therapy or clonal evolution.
  • CML in blast phase will be defined as greater than or equal to 30% blasts in the bone marrow or presence of extramedullary disease
  • Patients must have completed all previous anti-leukemic therapy for at least 2 weeks, except as noted, and have fully recovered from side effects of a previous therapy, unless disease progression necessitates early therapy. Patients may receive leukapheresis, hydroxyurea and anagrelide for up to 24 hours prior to start of study treatment. Patients receiving imatinib mesylate may continue to receive it uninterrupted, except for a 3-day window at treatment cycle 1.
  • Bilirubin less than or equal to 2 times the upper limit of normal (ULN); alanine aminotransferase (ALT) less than or equal to 3 times ULN; creatinine less than or equal to 1.5 times ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
  • Be able to comply with the requirements of the entire study
  • Be able and willing to provide written informed consent prior to any study related procedure
  • Patients and their partners must use an effective contraceptive during the study dosing period. The following are considered effective contraceptives: oral contraceptive pill, condom, diaphragm plus spermicide, abstinence, patient or partner surgically sterile, patient or partner more than 2 years post-menopausal, or injectable or implantable agent/device.

Exclusion Criteria:

  • New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension or congestive heart failure
  • Myocardial infarction in the previous 12 weeks
  • Other intercurrent illness which would preclude study conduct and assessment, including but not limited to another active malignancy, uncontrolled and active infection, positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) I/II status
  • Pregnant or lactating
  • Any medical or psychiatric condition which may compromise the ability to give written informed consent or to comply with the study protocol
  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: NCT00114959

Locations
United States, Texas
Univ. of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
ChemGenex Pharmaceuticals
Investigators
Study Director: Adam R Craig, M.D., PhD ChemGenex Pharmaceuticals
Principal Investigator: Jorge Cortes, M.D. Univ. of TX M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( ChemGenex Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00114959     History of Changes
Other Study ID Numbers: CGX-635-CML-201, MDACC protocol #2005-0067
Study First Received: June 20, 2005
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
ChemGenex Pharmaceuticals, Ltd
ChemGenex Pharmaceuticals
ChemGenex
Chronic Myeloid Leukemia
Myeloid Leukemia, Chronic
Leukemia
Myeloid Leukemia
Chronic Phase
Accelerated Phase
Blast Phase
Myeloid, Leukemia, Chronic, Accelerated Phase
Myeloid, Leukemia, Chronic
Leukemia, Myeloid, Chronic
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Chronic Phase
Leukemia, Myeloid, Accelerated-Phase
Myeloid, Leukemia, Chronic, Chronic Phase
Leukemia, Myeloid, Accelerated Phase
Homoharringtonine
Omacetaxine

Additional relevant MeSH terms:
Blast Crisis
Chronic Disease
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Chronic-Phase
Bone Marrow Diseases
Carcinogenesis
Cell Transformation, Neoplastic
Disease Attributes
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplastic Processes
Pathologic Processes
Harringtonines
Homoharringtonine
Imatinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014