Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000474954
Ethics application status
Approved
Date submitted
29/04/2011
Date registered
9/05/2011
Date last updated
9/05/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomised Phase III Study of Elacytarabine vs. Investigator’s
Choice in Patients with Late Stage Acute Myeloid Leukaemia
Scientific title
A Randomised Phase III Study in Patients with Late Stage Acute Myeloid Leukaemia, comparing the efficacy, measured as overall survival (OS), of elacytarabine and investigator’s choice.
Secondary ID [1] 253596 0
EudraCT No: 2009-014445-80
Secondary ID [2] 260074 0
FDA IND No: 68,282
Secondary ID [3] 260075 0
ClinicalTrials.gov identifier: NCT01147939
Universal Trial Number (UTN)
U1111-1119-4307
Trial acronym
CLAVELA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed / refractory AML 261152 0
Condition category
Condition code
Cancer 259311 259311 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Elacytarabine continous infusion days 1-5, every 3 weeks,
dose 2000 mg/m2/d.
1-2 treatment courses should be administered for remission induction, and 1-2 courses for consolidation. Patients who benefit from the treatment may receive repeated courses
of study drug at the discretion of the investigator, even if remission is not attained.
Intervention code [1] 258018 0
Treatment: Drugs
Comparator / control treatment
Investigator choice: One of the listed treatments must be selected prior to randomization: The formulation and dose will be at the discreation at the investigator / according to local standards and availibility
*Cytarabine at doses 1-6 g/m2/d, for up to 6 days, but with a maximum total dose; of 36 g/m2 per course (intravenous adm)
*Mitoxantrone + etoposide + cytarabine (MEC) (intravenous adm)
*Fludarabine + cytarabine + G-CSF +/- idarubicin (FLAG/FLAG-IDA) (intravenous adm):
*low-dose cytarabine; (intravenous adm maximum 20 mg/m2/d)
*hypomethylating agents (e.g. decitabine, azacitidine)(intravenous adm):
*Hydroxyurea with the intent to control the white blood cell count (WBC), (oral adm):
*Palliative care: Drugs / dose / adm at the discretion of the investigator
Control group
Active

Outcomes
Primary outcome [1] 262114 0
Compare the efficacy, measured as overall survival (OS), of elacytarabine and
investigator's choice in patients with late stage AML
Timepoint [1] 262114 0
Up to 6 months after last patient included in the trial.
Secondary outcome [1] 273189 0
Compare response rate and duration of response of elacytarabine and investigator's
choice in patients with late stage AML.
Remission rate measured by overall response rate (ORR); i.e. complete remission(CR) and complete remission with incomplete bone marrow recovery (CRi), Remission rate measured by CR, Remission duration analysed using cumulative incidence of relapse (CIR) measured
from date of CR or CRi
Timepoint [1] 273189 0
After completion of treatment according to protocol: Normally after 1-2 cycles of elacytarabine, for Investigator Choice Arm depending on type of control treatment selected
Secondary outcome [2] 273190 0
Compare the safety profile of elacytarabine with investigator's choice by assessing clinical and laboratory adverse events (AEs), and deaths.
Expected adverse events for elacytarabine is for example reduced blood counts, gastrointestinal ecents (diahorrea, constipation), fever, headache, elevated liver function tests
Timepoint [2] 273190 0
Up to 30 days after the last dose of study drug
Secondary outcome [3] 273191 0
Characterize exposure-response relationships for measures of effectiveness and toxicity by correlateing PK profiles with response and toxicity (for elacytarabine treated pateints only)
Timepoint [3] 273191 0
During and up to 48 hours after the first course of elacytarabine continous infusion

Eligibility
Key inclusion criteria
- Patients with a confirmed diagnosis of AML according to WHO classification
(excluding acute promyelocytic leukaemia) who have received two or three
previous induction/re-induction regimens. One of the (re-)induction regimens could
be stem cell transplantation (SCT) for achievement of remission. Maintenance and
consolidation (including SCT) may have been given, but are not counted as
previous regimens.
- Patient’s bone marrow aspirates and/or biopsies must contain > 5 % leukaemic
blast cells or patient must have biopsy-proven extramedullary AML, or patient’s
peripheral blood shows occurrence of leukaemic blast cells
- Patients must
a. have never attained CR or CRi (primary refractory), or
b. have failed initial induction therapy, and have attained CR or CRi after
salvage therapy(ies), and then relapsed within < 6 months, or
c. have attained CR or CRi after initial induction therapy and relapsed within
<12 months, and failed to respond to salvage therapy(ies), or
d. have relapsed after the latest CR or CRi within < 6 months
- Patients younger than 65 years should have received previous treatment with
cytarabine
- Patients must have recovered from previous bone marrow and/or stem cell
transplantation to a stage that the patient can tolerate the study treatment. There is
no restriction on number of regimens or type of treatment administered for
maintenance or consolidation during previous stages of the disease
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Persistent clinically significant toxicities from previous chemotherapy
-Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this
clinical study
- Active heart disease including myocardial infarction within previous 3 months,
symptomatic coronary artery disease, arrhythmias not controlled by medication, or
uncontrolled congestive heart failure. Any NYHA grade 3 or 4.
- Patients receiving any anti-leukaemic agents within the last 4 weeks. Hydroxyurea, however, is allowed for up to 12 hours prior to study treatment.
- Patients receiving any investigational treatment within the last 14 days

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Investigator will specify the intended control treatement prior to randomization.
Randomization will be centralized by an interactive web response system (IWRS)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Balanced block randomization will be performed.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/08/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
350
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment postcode(s) [1] 3962 0
3128
Recruitment postcode(s) [2] 3973 0
6009
Recruitment postcode(s) [3] 3974 0
3004
Recruitment postcode(s) [4] 3975 0
2065
Recruitment outside Australia
Country [1] 3180 0
Ireland
State/province [1] 3180 0
Country [2] 3181 0
Italy
State/province [2] 3181 0
Country [3] 3182 0
Norway
State/province [3] 3182 0
Country [4] 3183 0
Poland
State/province [4] 3183 0
Country [5] 3184 0
Romania
State/province [5] 3184 0
Country [6] 3185 0
Spain
State/province [6] 3185 0
Country [7] 3186 0
United Kingdom
State/province [7] 3186 0
Country [8] 3187 0
United States of America
State/province [8] 3187 0
Country [9] 3188 0
Belgium
State/province [9] 3188 0
Country [10] 3189 0
Germany
State/province [10] 3189 0
Country [11] 3190 0
Canada
State/province [11] 3190 0
Country [12] 3191 0
France
State/province [12] 3191 0

Funding & Sponsors
Funding source category [1] 258483 0
Commercial sector/Industry
Name [1] 258483 0
Clavis Pharma ASA
Country [1] 258483 0
Norway
Primary sponsor type
Commercial sector/Industry
Name
Clavis Pharma ASA
Address
Parkveien 53 B
0256 Oslo
Country
Norway
Secondary sponsor category [1] 264062 0
Commercial sector/Industry
Name [1] 264062 0
Trident Clinical Research Ltd
Address [1] 264062 0
Suite 2.09, 12 Cato Street
Hawthorn East, VIC, 3123
Country [1] 264062 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266937 0
Northern Sydney Central Coast Ethics Committee
Ethics committee address [1] 266937 0
Ethics committee country [1] 266937 0
Australia
Date submitted for ethics approval [1] 266937 0
06/01/2011
Approval date [1] 266937 0
29/03/2011
Ethics approval number [1] 266937 0
HREC/11/HAWKE/6
Ethics committee name [2] 266938 0
Sir Charles Gairdner Group Human Research Ethics Committee
Ethics committee address [2] 266938 0
Ethics committee country [2] 266938 0
Australia
Date submitted for ethics approval [2] 266938 0
23/11/2010
Approval date [2] 266938 0
31/03/2011
Ethics approval number [2] 266938 0
Ethics committee name [3] 266939 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [3] 266939 0
Ethics committee country [3] 266939 0
Australia
Date submitted for ethics approval [3] 266939 0
02/10/2010
Approval date [3] 266939 0
16/02/2011
Ethics approval number [3] 266939 0
Ethics committee name [4] 266978 0
Western Institutional Review Board (WIRB)
Ethics committee address [4] 266978 0
Ethics committee country [4] 266978 0
United States of America
Date submitted for ethics approval [4] 266978 0
Approval date [4] 266978 0
18/05/2010
Ethics approval number [4] 266978 0
1117637
Ethics committee name [5] 266985 0
Clinical Research Ethics Committee Agencia Valenciana de Salud
Ethics committee address [5] 266985 0
Ethics committee country [5] 266985 0
Spain
Date submitted for ethics approval [5] 266985 0
Approval date [5] 266985 0
07/06/2010
Ethics approval number [5] 266985 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32204 0
Address 32204 0
Country 32204 0
Phone 32204 0
Fax 32204 0
Email 32204 0
Contact person for public queries
Name 15451 0
Athos Gianella-Borradori
Address 15451 0
Clavis Pharma ASA
Parkveien 53 B
0256 Oslo
Country 15451 0
Norway
Phone 15451 0
+47 24 11 09 50
Fax 15451 0
+47 24 11 09 51
Email 15451 0
[email protected]
Contact person for scientific queries
Name 6379 0
Tove Flem Jacobsen
Address 6379 0
Clavis Pharma ASA
Parkveien 53 B
0256 Oslo
Country 6379 0
Norway
Phone 6379 0
+47 24 11 09 50
Fax 6379 0
+47 24 11 09 51
Email 6379 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
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