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Trial registered on ANZCTR


Registration number
ACTRN12609000377235
Ethics application status
Approved
Date submitted
4/03/2009
Date registered
28/05/2009
Date last updated
16/07/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Open Label Study of Subcutaneous Omacetaxine in Patients With Advanced Chronic Myeloid Leukemia.
Scientific title
A Phase II Open-Label Study of the Subcutaneous Administration of Omacetaxine in the Treatment of Patients With Chronic Myeloid Leukemia (CML) Who Have Failed or Are Intolerant to Tyrosine Kinase Inhibitor Therapy.
Secondary ID [1] 820 0
CGX-635-CML-203 (ChemGenex Pharmaceuticals)
Secondary ID [2] 856 0
ClinicalTrials.gov, NCT00462943
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 4420 0
Condition category
Condition code
Cancer 4684 4684 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Omacetaxine mepesuccinate
Patient will be treated with omacetaxine in treatment cycles of 28 days duration. There will be no breaks between treatment cycles and the cycles will continue for upto 24 months.
Dose = 1.25 mg/m2 twice daily for 14 days during induction and 1.25 mg/m2 twice daily for 7 days during maintenance)
Duration: Induction upto 6 months; maintenance upto 18 months (total of 24 months)
Mode of administration is Subcutaneous injection
Intervention code [1] 4162 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 5550 0
Proportion of patients achieving clinical response as assessed by blood tests to determine peripheral blood counts (hematology) and bone marrow biopsies for cytogenetic evaluations.
Timepoint [1] 5550 0
From commencement of treatment to last follow up. Last follow up will occur after 24 months of treatment, or earlier if the patient is withdrawn prior to study completion.
Blood tests wil be conducted prior to each treatment cycle (every month) and the bone marrow biopsies will be performed every 3 months while on study.
Primary outcome [2] 5551 0
Tolerance and toxicity of Omacetaxine as assessed by physical examinations, vial signs, blood tests and collection of adverse event information.
Timepoint [2] 5551 0
Assessed at least every month from commencement of treatment until last follow up at regular intervals. Last follow up will occur after 24 months of treatment, or earlier if the patient is withdrawn prior to study completion.
Secondary outcome [1] 9348 0
Degree of Hematologic Response as assessed by blood tests
Timepoint [1] 9348 0
Commencement of each treatment cycle.
Secondary outcome [2] 9349 0
Time to Response as assessed by blood tests and bone marrow biopsies.
Timepoint [2] 9349 0
From commence of treatment until the date of the first reported hematologic or cytogenetic response. Blood tests will be performed each month and boen marrow biospies will be conducted every 3 months from commencement of treatment.
Secondary outcome [3] 9350 0
Time to disease progression as assessed by blood tests and bone marrow biospies
Timepoint [3] 9350 0
From commence of treatment until death, development of accelerated-phase or blast-crisis CML, or the loss of complete hematologic or major cytogenetic response. Blood tests will be performed each month and boen marrow biospies will be conducted every 3 months from commencement of treatment.
Secondary outcome [4] 9351 0
Survival
Timepoint [4] 9351 0
From commence of treatment until death or last day of follow up. The site will be notified of any patient deaths as they occur. Last follow up will occur after 24 months of treatment, or earlier if the patient is withdrawn prior to study completion.

Eligibility
Key inclusion criteria
1. Male or female patients, age 18 years or older
2. Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
3. 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).
4. Acceptable Renal and Liver Function
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
6. Sexually active patients and their partners must use an effective double barrier method of contraception.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition
2. Myocardial infarction in the previous 12 weeks.
3. Other concurrent illness which would preclude study conduct and assessment uncontrolled and active infection, and positive human immunodeficiency virus (HIV) or positive Human T-lymphotropic virus (HTLV) I/II status, whether on treatment or not.
4. Pregnant or lactating.
5. Any medical or psychiatric condition, which may compromise the ability to give written informed consent or to comply with the study protocol.
6. Lymphoid Ph+ blast crisis
7. Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 1531 0
3181
Recruitment outside Australia
Country [1] 1637 0
United States of America
State/province [1] 1637 0
Country [2] 1638 0
Canada
State/province [2] 1638 0
Country [3] 1639 0
France
State/province [3] 1639 0
Country [4] 1640 0
Germany
State/province [4] 1640 0
Country [5] 1641 0
United Kingdom
State/province [5] 1641 0
Country [6] 1642 0
Hungary
State/province [6] 1642 0
Country [7] 1643 0
Poland
State/province [7] 1643 0
Country [8] 1644 0
Singapore
State/province [8] 1644 0
Country [9] 1645 0
India
State/province [9] 1645 0

Funding & Sponsors
Funding source category [1] 4608 0
Commercial sector/Industry
Name [1] 4608 0
ChemGenex Pharmaceuticals Ltd
Address [1] 4608 0
Level 4, 199 Moorabool St
Geelong VIC 3220
Country [1] 4608 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
ChemGenex Pharmaceuticals Inc.
Address
3715 Haven Avenue
Suite 100
Menlo Park, CA 94025
Country
United States of America
Secondary sponsor category [1] 4156 0
None
Name [1] 4156 0
Address [1] 4156 0
Country [1] 4156 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6654 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 6654 0
The Alfred Ethics Office
Second Floor, East Block,
The Alfred Hospital
Commercial Rd
Melbourne VIC 3181
Ethics committee country [1] 6654 0
Australia
Date submitted for ethics approval [1] 6654 0
Approval date [1] 6654 0
05/11/2008
Ethics approval number [1] 6654 0
247/08

Summary
Brief summary
This study looks at the effectiveness of chemotherapy with the drug Omacetaxine in people with chronic myeloid leukemia (CML).

Who is it for?
You can join this study if you have chronic myeloid leukemia (CML) (cancer of blood cells) which is in chronic, accelerated, or blast phase and you have have had no success with or have been intolerant to therapy with tyrosine kinase inhibitors (iminitab - Glivec).

Trial details
All participants will be treated with induction course cycles consisting of subcutaneous (SC) Omacetaxine administered twice daily for 14 consecutive days every 28 days. During this induction therapy, participants will be evaluated every 7 days with complete blood and platelet counts; the number of consecutive dose s of Omacetaxine or intervals between subsequent cycles may be adjusted as necessary, according to guidelines provided in the treatment plan.

Omacetaxine causes programmed cell death in myeloid cancer cells. Patients will be monitored from the beginning of treatment until any return of the disease or until they die. The study aims to measure the effectiveness of treatment, and investigates the tolerance to and toxicity of Omacetaxine.
Trial website
www.chemgenex.com
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29352 0
Address 29352 0
Country 29352 0
Phone 29352 0
Fax 29352 0
Email 29352 0
Contact person for public queries
Name 12599 0
Associate Professor Anthony Schwarer
Address 12599 0
Bone Marrow Transplant Programme
The Alfred Hospital
Commercial Rd
Melbourme VIC 3181
Country 12599 0
Australia
Phone 12599 0
+61 3 9276-3451
Fax 12599 0
Email 12599 0
a.schwarer@alfred.org.au
Contact person for scientific queries
Name 3527 0
Dr Adam Craig, M.D.
Address 3527 0
ChemGenex Pharmaceuticals Inc
3715 Haven Avenue, Suite 100
Menlo Park, CA 94025
Country 3527 0
United States of America
Phone 3527 0
+1 800-877-3009 ext 121
Fax 3527 0
Email 3527 0
acraig@chemgenex.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary