Clinical trial NCT00462943: Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML
Official title: A Phase II Open-Label Study of the Subcutaneous Administration of Homoharringtonine. (Omacetaxine Mepesuccinate; OMA) in the Treatment of Patients With Chronic Myeloid. Leukemia (CML) Who Have Failed or Are Intolerant to Tyrosine Kinase Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Keywords: CML
HHT
Homoharringtonine
Omacetaxine
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cephalon
name: ChemGenex Pharmaceuticals
First posted: 2007-04-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
timeFrame: Day 1 up to 6 months
measure: Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population
timeFrame: Day 1 up to 9 months
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total
timeFrame: up to 4 years
Secondary outcomes:
measure: Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)
timeFrame: Day 1 up to Month 9
measure: Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS
timeFrame: Day 1 up to Month 6
measure: Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL
timeFrame: Day 1 up to Month 6
measure: Percentage of Participants in Each Hematologic Response Category
timeFrame: Day 1 up to Month 6
measure: Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response
timeFrame: Day 1 up to Month 9
measure: Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL
timeFrame: Day 1 up to Month 9
measure: Number of Treatment Cycles Needed to Achieve Best Hematologic Response
timeFrame: Day 1 up to Month 6
measure: Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response
timeFrame: Day 1 up to Month 9
measure: Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response
timeFrame: Day 1 up to Month 6
measure: Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response
timeFrame: Day 1 up to Month 9
measure: Kaplan-Meier Estimates for Duration of Best Hematologic Response
timeFrame: up to four years
measure: Kaplan-Meier Estimates for Duration of Best Cytogenetic Response
timeFrame: up to four years
measure: Kaplan-Meier Estimates for Time to Disease Progression
timeFrame: up to 4 years
measure: Kaplan-Meier Estimates for Overall Survival
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Teva Investigational Site 303
state: California
city: Beech Grove
country: United States
facility: Teva Investigational Site 308
state: Indiana
city: Baltimore
country: United States
facility: Teva Investigational Site 311
state: Maryland
city: Bronx
country: United States
facility: Teva Investigational Site 302
state: New York
city: Buffalo
country: United States
facility: Teva Investigational Site 305
state: New York
city: Philadelphia
country: United States
facility: Teva Investigational Site 310
state: Pennsylvania
city: Houston
country: United States
facility: Teva Investigational Site 301
state: Texas
city: Seattle
country: United States
facility: Teva Investigational Site 314
state: Washington
city: Montreal
country: Canada
facility: Teva Investigational Site 313
city: Toronto
country: Canada
facility: Teva Investigational Site 309
city: Bordeaux
country: France
facility: Teva Investigational Site 329
city: Le Chesnay Cedex
country: France
facility: Teva Investigational Site 321
city: Lille
country: France
facility: Teva Investigational Site 322
city: Lyon Cedex 03
country: France
facility: Teva Investigational Site 320
city: Nice
country: France
facility: Teva Investigational Site 324
city: Paris
country: France
facility: Teva Investigational Site 328
city: Poitiers Cedex
country: France
facility: Teva Investigational Site 323
city: Strasbourg
country: France
facility: Teva Investigational Site 327
city: Toulouse
country: France
facility: Teva Investigational Site 325
city: Berlin
country: Germany
facility: Teva Investigational Site 331
city: Mannheim
country: Germany
facility: Teva Investigational Site 330
city: Budapest
country: Hungary
facility: Teva Investigational Site 350
city: Hyderabad
country: India
facility: Teva Investigational Site 371
city: Mumbai
country: India
facility: Teva Investigational Site 370
city: Bologna
country: Italy
facility: Teva Investigational Site 390
city: Gdansk
country: Poland
facility: Teva Investigational Site 360
city: Warszawa
country: Poland
facility: Teva Investigational Site 361
city: Singapore
country: Singapore
facility: Teva Investigational Site 380
city: London
country: United Kingdom
facility: Teva Investigational Site 340
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jorge Cortes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cortes J, Digumarti R, Parikh PM, Wetzler M, Lipton JH, Hochhaus A, Craig AR, Benichou AC, Nicolini FE, Kantarjian HM; Omacetaxine 203 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. Am J Hematol. 2013 May;88(5):350-4. doi: 10.1002/ajh.23408. Epub 2013 Mar 7.