Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000373279
Ethics application status
Approved
Date submitted
4/03/2009
Date registered
27/05/2009
Date last updated
23/12/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Omacetaxine in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation
Scientific title
A multi-center phase II open-label study to evaluate the efficacy and safety of subcutaneous administration of omacetaxine in the treatment of patients with chronic myeloid leukemia (CML) in chronic, accelerated and blast phase who have tested positive for the T315I bcr-abl point mutation.
Secondary ID [1] 819 0
CGX-635-CML-202 (ChemGenex Pharmaceuticals)
Secondary ID [2] 857 0
ClinicalTrials.gov, NCT00375219
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 4419 0
Condition category
Condition code
Cancer 4683 4683 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Omacetaxine mepesuccinate
Patient will receive omacetaxine in treatment cycles. Each treatment cycle will have a duration of 28 days and treatment cycles will continue for upto 24 months - without a break between cycles.
Dose = 1.25 mg/m2 twice daily for the first 14 days during induction treatment cycles and 1.25 mg/m2 twice a day for the first 7 days during maintenance treatment cycles.
Duration: upto 6 months for induction and ~18 months for maintenance (total of 24 months on study).
Mode of administration is subcutaneous injection.
Patients will be follow up at least every month while on study (upto 24 months).
Intervention code [1] 4161 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 5548 0
Proportion of patients achieving clinical response as assessed by blood tests and bone marrow biospies.
Timepoint [1] 5548 0
From commencement of treatment to last follow up. Blood tests will be conducted at least every month and the bone marrow biospies will be conducted every 3 months following commencement of treatment.
Last follow up will occur after 24 months of treatment, or earlier if the patient is withdrawn prior to study completion.
Primary outcome [2] 5549 0
Tolerance and toxicity of Omacetaxine as assessed by physical examinations, vital signs, blood tests an adverse event reporting.
Timepoint [2] 5549 0
From commencement of treatment until last follow up at least on a monthly basis. Last follow up will occur after 24 months of treatment, or earlier if the patient is withdrawn prior to study completion.
Secondary outcome [1] 9344 0
Degree of Hematologic Response as assessed by blood tests
Timepoint [1] 9344 0
Commencement of each treatment cycle
Secondary outcome [2] 9345 0
Time to Response as assessed by blood test and bone marrow biospies
Timepoint [2] 9345 0
At least every month from commence of treatment until the date of the first reported hematologic or cytogenetic response.
Secondary outcome [3] 9346 0
Time to progression as assessed by blood tests and bone marrow biopsies
Timepoint [3] 9346 0
At least every month from commence of treatment until death, development of accelerated-phase or blast-crisis CML, or the loss of complete hematologic or mayor cytogenetic response
Secondary outcome [4] 9347 0
Survival
Timepoint [4] 9347 0
Continously (a minimum of monthly) from commencement of treatment until death or last day of follow up. Last follow up will occur after 24 months of treatment, death 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. The patient will have the T315I BCR-ABL gene mutation.

4. Patients will have failed prior imatinib therapy.

5. Acceptable Renal and Liver Function.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

7. Sexually active patients and their partners must use an effective double barrier method of contraception.
Minimum age
18 Years
Maximum age
No limit
Sex
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 such as angina pectoris, clinically significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension or congestive heart failure
Myocardial infarction in the previous 12 weeks.

2. Lymphoid Ph+ blast crisis.

3. Pregnant or lactating.

4. Any medical or psychiatric condition, which may compromise the ability to give written informed consent or to comply with the study protocol.

5. Patient is candidate (and has a donor identified) for bone marrow or blood stem cell transplantation.

6. 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
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
11/03/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 1530 0
3181
Recruitment outside Australia
Country [1] 1609 0
United Kingdom
State/province [1] 1609 0
London
Country [2] 1610 0
United States of America
State/province [2] 1610 0
Indiana
Country [3] 1611 0
United States of America
State/province [3] 1611 0
New York
Country [4] 1612 0
United States of America
State/province [4] 1612 0
Massachusetts
Country [5] 1613 0
United States of America
State/province [5] 1613 0
Georgia
Country [6] 1614 0
United States of America
State/province [6] 1614 0
Pennsylvania
Country [7] 1615 0
United States of America
State/province [7] 1615 0
Texas
Country [8] 1616 0
United States of America
State/province [8] 1616 0
Maryland
Country [9] 1617 0
Canada
State/province [9] 1617 0
Ontario
Country [10] 1618 0
Canada
State/province [10] 1618 0
Quebec
Country [11] 1619 0
France
State/province [11] 1619 0
Lyon
Country [12] 1620 0
France
State/province [12] 1620 0
Le Chesnay
Country [13] 1621 0
France
State/province [13] 1621 0
Lille
Country [14] 1622 0
France
State/province [14] 1622 0
Poitiers
Country [15] 1623 0
France
State/province [15] 1623 0
Vandoeuvre
Country [16] 1624 0
France
State/province [16] 1624 0
Nice
Country [17] 1625 0
France
State/province [17] 1625 0
Toulouse
Country [18] 1626 0
France
State/province [18] 1626 0
Strasbourg
Country [19] 1627 0
France
State/province [19] 1627 0
Paris
Country [20] 1628 0
France
State/province [20] 1628 0
Bordeaux
Country [21] 1629 0
Germany
State/province [21] 1629 0
Mannheim
Country [22] 1630 0
Germany
State/province [22] 1630 0
Berlin
Country [23] 1631 0
Hungary
State/province [23] 1631 0
Budapest
Country [24] 1632 0
Poland
State/province [24] 1632 0
Gdansk
Country [25] 1633 0
Poland
State/province [25] 1633 0
Warsaw
Country [26] 1634 0
Singapore
State/province [26] 1634 0
Singapore City
Country [27] 1635 0
India
State/province [27] 1635 0
Mumbai
Country [28] 1636 0
India
State/province [28] 1636 0
Hyderabad

Funding & Sponsors
Funding source category [1] 4607 0
Commercial sector/Industry
Name [1] 4607 0
ChemGenex Pharmaceuticals Ltd
Country [1] 4607 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] 4155 0
None
Name [1] 4155 0
Address [1] 4155 0
Country [1] 4155 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6653 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 6653 0
The Alfred Ethics Office
Second Floor, East Block,
The Alfred Hospital
Commercial Rd
Melbourne VIC 3181
Ethics committee country [1] 6653 0
Australia
Date submitted for ethics approval [1] 6653 0
Approval date [1] 6653 0
05/11/2008
Ethics approval number [1] 6653 0
246/08

Summary
Brief summary
This study looks at the effectiveness of chemotherapy with the drug Omacetaxine in people with chronic myeloid leukemia (CML) who have the Philadelphia chromosome (T315I bcr-abl gene) mutation.


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
- tested positive for the T315I bcr-abl point mutation
- had no success with tyrosine kinase inhibitor (iminitab - Glivec) treatment.


Trial details
All participants will be treated with induction course cycles consisting of subcutaneous Omacetaxine administered twice daily for 14 consecutive days every 28 days. Participants who demonstrate a response may receive maintenance therapy for up to 24 months, consisting of subcutaneous Omacetaxine twice daily for 7 days every 28 days. Participants will be evaluated every 7 days with complete blood and platelet counts while undergoing therapy; the number of consecutive doses 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
J. Cortes. Safety and Efficacy of Subcutaneous Omacetaxine Mepesuccinate in imatinib-resistant chronic myeloid leukemia patients with the T315I mutation – Results on an ongoing multicentre phase 2/3 study. American Society of Hematology (ASH) 50th Annual Meeting in San Francisco, California. Abstract # 3239. 09 Dec 2008.

J.Cortes. Data from a multicentre open label study of subcutaneous (SC) omacetaxine mepesucinate (OMA) in imatinib (IM) resistant chronic myeloid leukemia (CML) patients (PTS) with the T315I mutation. European Hematology Association (EHA) Annual Congress in Copenhagen, Denmark. Abstract 0123. 13 June 2008.

A. Benichou. Multicenter open label study of subcutaneous (SC) omacetaxine (OMA) in imatinib (IM)-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation. American Society of Clinical Oncology (ASCO) 44th Annual Meeting in Chicago, Illinois. Abstract No: 7021. 03 June 2008.
Public notes

Contacts
Principal investigator
Name 29351 0
Address 29351 0
Country 29351 0
Phone 29351 0
Fax 29351 0
Email 29351 0
Contact person for public queries
Name 12598 0
Associate Professor Anthony Schwarer
Address 12598 0
Associate Professor Anthony Schwarer
Bone Marrow Transplant Programme
The Alfred Hospital
Commercial Rd
Melbourne VIC 3181
Country 12598 0
Australia
Phone 12598 0
+61 3 9276-3451
Fax 12598 0
Email 12598 0
[email protected]
Contact person for scientific queries
Name 3526 0
Dr Adam Craig, M.D.
Address 3526 0
ChemGenex Pharmaceuticals Inc
3715 Haven Avenue, Suite 100
Menlo Park, CA 94025
Country 3526 0
United States of America
Phone 3526 0
+1 800-877-3009 ext 121
Fax 3526 0
Email 3526 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.