Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML

This study has been completed.
Sponsor:
Collaborators:
Cephalon
ChemGenex Pharmaceuticals
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT00462943
First received: April 17, 2007
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

A Phase II open-label trial of subcutaneous HHT (omacetaxine mepesuccinate) in the treatment of patients who are resistant to or intolerant to Tyrosine Kinase Inhibitors.


Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: Omacetaxine mepesuccinate
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 Subcutaneous Administration of Homoharringtonine (Omacetaxine Mepesuccinate) in the Treatment of Patients With Chronic Myeloid Leukemia (CML) Who Have Failed or Are Intolerant to Tyrosine Kinase Inhibitor Therapy

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Percentage of Participants Achieving a Clinical Response by Subpopulation [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    Subpopulations reflect chronic myeloid leukemia (CML) phases: chronic, accelerated, and blast phase.

  • Participants with Adverse Events by Subpopulation [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
    Subpopulations reflect chronic myeloid leukemia (CML) phases: chronic, accelerated, and blast phase.


Secondary Outcome Measures:
  • Time to Response [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
    The time from the initiation of treatment until the date of first reported hematologic or cytogenetic response.

  • Duration of Response [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    The time from the first reported date of hematologic or cytogenetic response, as defined above, until the earliest date of objective evidence of disease progression, relapse or death.

  • Time to Disease Progression [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    The time from the initiation of treatment until the onset date of death, the development of accelerated-phase or blast-crisis CML, or the loss of complete hematologic or major cytogenetic response, whichever comes first.

  • Overall Survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    The time from the initiation of treatment until death from any cause or the last day of patient contact or evaluation for patients that are lost to follow-up.

  • Participants' Degree of Suppression of the Philadelphia Chromosome (Ph) [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Participants' Degree of Suppression of BCR-ABL transcript levels [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Percentage of CML Participants with Accelerated or Blast Phase Who Return to Chronic Phase [ Time Frame: Up to four years ] [ Designated as safety issue: No ]
  • Percentage of CML Participants with Accelerated or Blast Phase Who Show No Evidence of Leukemia [ Time Frame: up to four years ] [ Designated as safety issue: No ]
  • Percentage of Participants with Extramedullary Disease (EMD) at Baseline Who Achieve a Clinical Response [ Time Frame: up to four years ] [ Designated as safety issue: No ]
  • The Number of Induction Cycles to Achieve a Clinical Response [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: March 2007
Study Completion Date: September 2013
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OMA

Omacetaxine mepesuccinate (OMA) Induction: 1.25mg/m^2 subcutaneously twice daily for 14 consecutive days, every 28 days.

Omacetaxine mepesuccinate (OMA) Maintenance: 1.25mg/m^2 subcutaneously twice daily for 7 consecutive days, every 28 days.

Drug: Omacetaxine mepesuccinate

Induction: 1.25mg/m^2 subcutaneously twice daily for 14 consecutive days, every 28 days.

Maintenance: 1.25mg/m^2 subcutaneously twice daily for 7 consecutive days, every 28 days.

Response targets during induction vary by chronic myeloid leukemia (CML) subclass (chronic, accelerated, or blast phase). Participants will complete at least one cycle (14 days treatment of a 28 day cycle) of induction therapy before changing to maintenance therapy. Participants not demonstrating evidence of clinical response after 6 induction cycles will be considered for removal from the study.

Other Names:
  • Homoharringtonine
  • HHT

Detailed Description:

This will be an open label, multicenter study of subcutaneous HHT (omacetaxine mepesuccinate) therapy of patients with chronic myeloid leukemia (CML) in chronic, accelerated, or blast phase who have failed or are intolerant to tyrosine kinase inhibitor therapy. Patients will be treated with induction course cycles consisting of subcutaneous (SC) HHT 1.25 mg/m² twice daily for 14 consecutive days every 28 days. Patients will be evaluated every 7 days with complete blood and platelet counts while undergoing induction therapy; the number of consecutive doses of HHT or intervals between subsequent cycles may be adjusted, as clinically indicated, according to guidelines provided in the treatment plan.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients, age 18 years or older
  • Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
  • Patients will have either failed, demonstrated intolerance, or a combination of prior failure and intolerance, to prior treatments with at least two tyrosine kinase inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a response) or secondary resistance (loss of response).
  • Acceptable Renal and Liver Function
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Sexually active patients and their partners must use an effective double barrier method of contraception

Exclusion Criteria:

  • New York Heart Association classification (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition
  • Myocardial infarction in the previous 12 weeks.
  • Other concurrent illness which would preclude study conduct and assessment
  • uncontrolled and active infection, and positive HIV or positive HTLV I/II status, whether on treatment or not.
  • 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.
  • Lymphoid Ph+ blast crisis
  • Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00462943

  Show 28 Study Locations
Sponsors and Collaborators
Teva Pharmaceutical Industries
Cephalon
ChemGenex Pharmaceuticals
Investigators
Principal Investigator: Jorge Cortes, MD M.D. Anderson Cancer Center
  More Information

No publications provided by Teva Pharmaceutical Industries

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT00462943     History of Changes
Other Study ID Numbers: CGX-635-CML-203, 2007-001286-15
Study First Received: April 17, 2007
Last Updated: September 23, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Europe: European Medicines Evaluation Agency
United Kingdom: Medicines Control Agency
India: Drugs Controller General of India
Singapore: Health Sciences Authority

Keywords provided by Teva Pharmaceutical Industries:
CML
HHT
Homoharringtonine
Omacetaxine

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Homoharringtonine
Harringtonines
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014