Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation

This study has been completed.
Sponsor:
Collaborators:
Cephalon
ChemGenex Pharmaceuticals
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT00375219
First received: September 8, 2006
Last updated: September 23, 2013
Last verified: September 2013

September 8, 2006
September 23, 2013
September 2006
December 2010   (final data collection date for primary outcome measure)
  • 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 3 years ] [ Designated as safety issue: Yes ]
    Subpopulations reflect chronic myeloid leukemia (CML) phases: chronic, accelerated, and blast phase.
Hematologic and cytogenetic response rates, respectively
Complete list of historical versions of study NCT00375219 on ClinicalTrials.gov Archive Site
  • 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 Participants Who Showed a Hematological Improvement [ 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 3 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 3 years ] [ Designated as safety issue: No ]
  • Percentage of Participants with Extramedullary Disease (EMD) at Baseline Who Achieve a Clinical Response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Had a Significant Reduction of the Proportion of T315I Mutated BCR-ABL [ Time Frame: up to 3 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 ]
  • Time to Response [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Time to disease progression [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation
A Phase II Open-Label Study of the Subcutaneous Administration of Homoharringtonine (Omacetaxine Mepesuccinate) in the Treatment of Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation

To evaluate the safety and efficacy of subcutaneous administration of omacetaxine mepesuccinate (HHT) in achieving a clinical response in CML patients in chronic, accelerated, or blast phase who have failed prior imatinib therapy and have the T315I kinase domain gene mutation.

Point mutations within the ABL kinase domain of the BCR-ABL gene are emerging as the most frequent mechanism for resistance to imatinib and resultant reactivation of kinase activity. The risk of mutation development is particularly high in patients who are beyond chronic phase, as well as those with a long duration of disease prior to imatinib therapy.

The T315I kinase domain (KD) point mutation has merited particular attention, as T315I expressing CML cells are markedly resistant to imatinib. CML patients with the T315I KD mutation, therefore, do not respond to continued treatment with imatinib, and preliminary clinical data indicate that neither of two newer tyrosine kinase inhibitors will have activity in patients with T315I KD mutation either.

Omacetaxine mepesuccinate (HHT) is a potent inducer of apoptosis (programmed cell death) in myeloid cells and inhibits angiogenesis (blood vessel formation). In Phase 2 studies, HHT has demonstrated clinical activity in patients with CML, both as a single agent and in-combination with other chemotherapeutic drugs. HHT works via a different mechanism than imatinib or other tyrosine kinase inhibitors (TKI's), and HHT has been shown to inhibit in vitro CML cell lines which harbor the T315I KD mutation and are highly resistant to imatinib. Therefore, CML patients who have the T315I KD mutation may still respond to treatment with HHT. HHT may therefore be an attractive therapeutic option for patients with the T315I KD mutation.

On this basis, a multicenter clinical trial is being conducted of HHT therapy for CML patients who have failed prior imatinib therapy and have the T315I KD mutation.

Patients will be treated with an induction course consisting of subcutaneous (SC) HHT twice daily for 14 consecutive days every 28 days. Patients who demonstrate a response, may receive maintenance therapy for up to 24 months, consisting of subcutaneous (SC) HHT twice daily for 7 days every 28 days.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Myeloid Leukemia
Drug: Omacetaxine mepesuccinate

Induction:

1.25 mg/m^2 subcutaneously, twice daily for 14 consecutive days every 28 days until response. Patients not demonstrating evidence of clinical response after 6 induction cycles will be considered for removal from the study.

Maintenance:

1.25 mg/m^2 subcutaneously, twice daily for 7 consecutive days in a 28-day cycle, for up to 2 years.

Other Names:
  • Homoharringtonine
  • OMA
  • SynriboTM
  • HHT
Experimental: OMA

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

Maintenance: 1.25 mg/m^2 subcutaneously, twice daily for 7 consecutive days of every 28-day cycle for up to two years.

Intervention: Drug: Omacetaxine mepesuccinate
Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, Kantarjian H; Omacetaxine 202 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-80. Epub 2012 Aug 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
103
September 2013
December 2010   (final data collection date for primary outcome measure)

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
  • The patient will have the T315I BCR-ABL gene mutation
  • Patients will have failed prior imatinib therapy
  • ECOG performance status 0-2

Exclusion Criteria:

  • 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
  • Lymphoid Ph+ blast crisis
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   France,   Germany,   Hungary,   India,   Italy,   Poland,   Singapore,   United Kingdom
 
NCT00375219
CGX-635-CML-202, 2006-000176-32
Yes
Teva Pharmaceutical Industries
Teva Pharmaceutical Industries
  • Cephalon
  • ChemGenex Pharmaceuticals
Principal Investigator: Jorge Cortes, MD Univ. of Texas M.D. Anderson Cancer Center
Principal Investigator: Andreas Hochhaus, MD Prof Dr Mannheim der Universitat Heidelberg
Teva Pharmaceutical Industries
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP