Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000514505
Ethics application status
Not yet submitted
Date submitted
24/11/2006
Date registered
12/12/2006
Date last updated
14/09/2007
Type of registration
Prospectively registered

Titles & IDs
Public title
A research study for patients with acute myeloid leukemia (AML) in first relapse
Scientific title
A Phase III Randomized Study of Cloretazine (VNP40101M) and Cytosine Arabinoside (AraC) in Patients with Acute Myeloid Leukemia in First Relapse to Improve the Overall Remission Rate
Secondary ID [1] 323 0
Vion: CLI-037
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 1491 0
Condition category
Condition code
Cancer 1588 1588 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A double-blind placebo-controlled phase III randomised multi-center study with Cloretazine (VNP40101M) and Cytosine Arabinoside (AraC).

The total duration of the interventions is 3 days. This includes 3 days of AraC and one 30-60 minutes infusion of Cloretazine (VNP40101M) or placebo on Day 2 as described below:

Intervention Group:
• AraC is administered at a dose of 1.5 gm/m2/day on Days 1-3 as a continuous infusion over 24 hrs.
• Cloretazine (VNP40101M) at a dose of 600 mg/m2 is given on Day 2 over 30-60 minutes in an infusion of 5% Dextrose Injection, USP (United States Pharmacopeia).

Blinding:
The pharmacist will be unblinded. The subject, therapist, assessor and data analyst will remain blinded. An interim analysis is planned after the first 210 accrued patients.

Criteria for Re-Treatment and Consolidation:

(Glossary: Complete Response or Remission (CR).
Complete Response p (CRp) is defined as meeting all criteria for CR except recovery of platelet counts to >100,000 uL)

Patients with evidence of clinical progression are not eligible to receive additional protocol treatment. Patients without evidence of clinical progression, who have not achieved at least a CRp, may receive a second induction cycle, no earlier than day 35 and no later than day 60.

Patients who attain at least a CRp after the first or second induction cycle will be eligible for one cycle of consolidation. Consolidation should begin within 6 weeks after initial documentation of CR or CRp. Patients will receive Cloretazine (VNP40101M)/AraC or placebo/AraC according to their original assignment.
Intervention code [1] 1463 0
Treatment: Drugs
Comparator / control treatment
Control Group:
• AraC is administered at a dose of 1.5 gm/m2/day on Days 1-3 as a continuous infusion over 24 hrs.
• An infusion of 5% Dextrose Injection, USP is given on Day 2 over 30-60 minutes.
Control group
Placebo

Outcomes
Primary outcome [1] 2192 0
The primary endpoint is overall response (CR and CRp) rate (ORR).
CRp is defined as meeting all criteria for CR except recovery of platelet counts to >100,000 uL.
Timepoint [1] 2192 0
After treatment, patients will be seen at least once weekly with at least twice weekly labs until a CR or CRp, or non-response/ progression is documented.
Secondary outcome [1] 3822 0
Time-to-progression or death from any cause; duration of response; survival; and toxicity.
Timepoint [1] 3822 0
All patients enrolled in the study will enter a follow-up phase after study completion/early withdrawal. For patients who respond, data regarding disease status will be collected until recurrence for up to 3 years. Data regarding survival will also be collected for up to 3 years. Follow-up evaluations are recommended every 3 months. End of study will be defined as 3 years following enrolment of the last study patient.

Eligibility
Key inclusion criteria
Patients must have AML (any WHO classification excluding acute promyelocytic leukemia) in first relapse after a first CR (complete response) or CRp (meeting all criteria for CR except recovery of platelet counts to >100,000 uL) determined by bone marrow aspirates and/or biopsies that contain = 10% blasts. The duration of first CR or CRp must have been at least 3 months but less than 24 months, calculated from the day CR or CRp was documented following the initial induction regimen to the day leukemia relapse was confirmed by recurrence of blasts in peripheral blood, bone marrow histopathology and/or histological proven central nervous system (CNS) or extramedullary disease.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Uncontrolled active infection of any kind. Presence of any other severe medical condition that may compromise the safety of treatment.

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)
Central randomisation by phone/fax
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The pharmacist will be unblinded. The subject, therapist, assessor and data analyst will remain blinded.
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
420
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 423 0
United States of America
State/province [1] 423 0
Country [2] 424 0
United Kingdom
State/province [2] 424 0
Country [3] 425 0
Canada
State/province [3] 425 0
Country [4] 426 0
Belgium
State/province [4] 426 0
Country [5] 427 0
Germany
State/province [5] 427 0
Country [6] 428 0
Poland
State/province [6] 428 0
Country [7] 429 0
Greece
State/province [7] 429 0
Country [8] 430 0
France
State/province [8] 430 0
Country [9] 431 0
Netherlands
State/province [9] 431 0
Country [10] 432 0
Germany
State/province [10] 432 0

Funding & Sponsors
Funding source category [1] 1733 0
Commercial sector/Industry
Name [1] 1733 0
Vion Pharmaceuticals, Inc.
Country [1] 1733 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Vion Pharmaceuticals, Inc.
Address
Four Science Park
New Haven, CT 06511
Country
United States of America
Secondary sponsor category [1] 1527 0
None
Name [1] 1527 0
N/A
Address [1] 1527 0
Country [1] 1527 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 3200 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 3200 0
1 St Andrews Place East Melbourne 3002
Ethics committee country [1] 3200 0
Australia
Date submitted for ethics approval [1] 3200 0
30/09/2007
Approval date [1] 3200 0
Ethics approval number [1] 3200 0
Ethics committee name [2] 3201 0
Haematology Department Fremantle Hospital
Ethics committee address [2] 3201 0
Fremantle Hospital, Alma St. Western Australia 6160
Ethics committee country [2] 3201 0
Australia
Date submitted for ethics approval [2] 3201 0
Approval date [2] 3201 0
Ethics approval number [2] 3201 0
Ethics committee name [3] 3202 0
Oncology, Haematology & Radiation Unit Princess Alexandra Hospital
Ethics committee address [3] 3202 0
Princess Alexandra Hospital, Ipswich Road Woollongabba Queensland 4001
Ethics committee country [3] 3202 0
Australia
Date submitted for ethics approval [3] 3202 0
30/09/2007
Approval date [3] 3202 0
Ethics approval number [3] 3202 0
Ethics committee name [4] 3203 0
St. Vincent's Hospital Department of Haematology
Ethics committee address [4] 3203 0
St. Vincent's Hospital 41 Victoria Parade Fitzroy Victoria 3065
Ethics committee country [4] 3203 0
Australia
Date submitted for ethics approval [4] 3203 0
30/09/2007
Approval date [4] 3203 0
Ethics approval number [4] 3203 0
Ethics committee name [5] 3204 0
Andrew Love Cancer Centre
Ethics committee address [5] 3204 0
70 Swanston Street Geelong Victoria 3220
Ethics committee country [5] 3204 0
Australia
Date submitted for ethics approval [5] 3204 0
30/09/2007
Approval date [5] 3204 0
Ethics approval number [5] 3204 0

Summary
Brief summary
The investigational product in this trial is Cloretazine (VNP40101M). Cytosine Arabinoside (AraC) is a known treatment.
Currently, there is no known standard chemotherapy that is considered effective for patients with AML in first relapse.
With existing treatments, tumor reduction can be difficult to achieve and is short-lived. Vion Pharmaceuticals, Inc. is interested in developing new drugs that might have a better effect against the disease. Hence, there is a need for trials such as this.
This is a double-blind, randomised, two-arm, phase 3, placebo-controlled trial. For every six patients randomized on to this trial, four patients will receive study drug and two patients will receive placebo.
AraC will be given to one group of patients in combination with Cloretazine (VNP40101M) and the other group of patients will receive AraC with placebo.
The main clinical hypothesis under study is that the patients on the experimental arm have a higher overall response rate (ORR) compared to patients on the control arm, i.e., the main objective is to see if the group of patients with the Cloretazine (VNP40101M) added, do better than the group who receive AraC alone.
Patients with AML in first relapse will be invited to take part in this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27397 0
Address 27397 0
Country 27397 0
Phone 27397 0
Fax 27397 0
Email 27397 0
Contact person for public queries
Name 10652 0
Francis Séguy
Address 10652 0
41 rue des 3 Fontanot
Nanterre 92000
Country 10652 0
France
Phone 10652 0
+33 1 41398460
Fax 10652 0
+33 1 41398469
Email 10652 0
Francis.Seguy@i3research.com
Contact person for scientific queries
Name 1580 0
Dr. Melita Kenealy
Address 1580 0
Peter MacCallum Cancer Centre
1 St Andrews Place
East Melbourne VIC 3002
Country 1580 0
Australia
Phone 1580 0
+61 3 96561111
Fax 1580 0
+61 3 96561408
Email 1580 0
Melita.Kenealy@petermac.org

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No Supporting Document Provided


Results publications and other study-related documents

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