Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000970842
Ethics application status
Approved
Date submitted
14/03/2012
Date registered
10/09/2012
Date last updated
5/02/2020
Date data sharing statement initially provided
5/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An exploratory Phase I/II Clinical Evaluation of VAL-1000 in adults with Acute Leukaemias
Scientific title
An exploratory Phase I/II safety and tolerability clinical evaluation of VAL-1000 in adults with Acute Leukaemias
Secondary ID [1] 280126 0
None
Universal Trial Number (UTN)
Trial acronym
VAL-1000
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Leukaemias 286054 0
Condition category
Condition code
Cancer 286241 286241 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
100mg, 150mg, 200mg or 250mg VAL-1000 daily via oral administration for 12 months.

This is a 2-stage, Phase I/II (3 + 3 dose escalation with an expansion phase), open label, single centre study to determine the safety, tolerability and preliminary efficacy of escalating doses of oral VAL-1000.

Three patients will be enrolled per cohort, if a one of the three experience a Dose Limiting Toxicity (DLT) in the first 4 weeks (Cycle 1) then that patient will be taken off study and replaced by another three patients (ie 3 +3 design) if another pateint experiences a DLT then the dose below the DLT dose is the Maximum Tolerated Dose (MTD). If no DLT occur in Cycle 1 (first 4 weeks of treatment) then the second cohort at the next dose will be recruited.

Three patients will have a bone marrow aspirate to determine the baseline blast count and to collect samples for correlative laboratory studies. The first cohort of three patients will be treated daily with VAL-1000 50 mg orally twice daily (100mg/day) for 4 weeks. Patients experiencing a DLT or disease progression will be taken off study; other patients will continue to be treated with 50mg oral twice a day. VAL-1000. If no DLT occur then the next cohort will be recruited.

Three evaluable patients will be required at each treatment level. Escalation from a particular treatment level to the next treatment level will be allowed if during CYCLE 1 of induction therapy - no patients experience any dose limiting toxicities (DLT) i.e. any grade 3 or 4 non-haematological toxicity (NHT) considered to be caused by VAL-1000.

Once the Maximum Tolerated Dose (MTD) level has been identified, a dose expansion phase will continue recruiting patients at or below the MTD, until a total of 24 evaluable patients have been recruited.
Intervention code [1] 284457 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 286711 0
To examine the safety and tolerability of VAL-1000 in patients with acute Leukaemias. All subjects who receive at least one dose of study drug will be included in the safety analyses. This will be done by:
- Adverse events will be classified using the MedDRA classification system. The severity of the toxicities will be graded according to the NCI CTC V4 whenever possible.
- Each occurrence of an adverse event will be counted once (i.e. an event that covers multiple observations will be counted as a single event until it resolves; if the same adverse event occurs after the initial event has resolved, it will count as a separate event).
- Adverse events will be summarised by worst NCI CTC V4 grade.
- Laboratory data will be graded according to NCI CTC V4 severity grade
Timepoint [1] 286711 0
At the end of study
Secondary outcome [1] 296509 0
Patient related efficacy outcomes this will be done by the Principal Investigator using the following criteria:
- Assesing response ,PR/CR/CRi according to Cheson criteria (Cheson et al., 2003) in patients receiving at least 1 cycle (4 weeks) of treatment
- Progression-free survival (PFS)
- Overall survival (OS)
- Time to complete remission
Timepoint [1] 296509 0
At the end of study
Secondary outcome [2] 296510 0
To define a dose level for testing in subsequent phase II clinical trials. This will be done by cclinical assesment and adverse event profile.
Timepoint [2] 296510 0
At the end of study
Secondary outcome [3] 296511 0
To assess drug pharmacokinetics this will be done by blood analysis.
Timepoint [3] 296511 0
At the end of study

Eligibility
Key inclusion criteria
- Male and Female subjects 18 years of age and over with AML, ALL or high-risk MDS (IPSS greater than Int-2), who are unsuitable for treatment with standard chemotherapy regimens, e.g., elderly (greater than 70 yrs.), poor risk (e.g. adverse risk karyotype) or who have failed up to 3 lines of therapy.
- Ability to communicate with trial staff, understand the Trial Information Sheet and sign the written informed consent, willing to follow the protocol requirements and comply with protocol restrictions and procedures.
- Secondary AML (including therapy-related) are included
- Life expectancy of greater than 3 months in relation to diseases other than AML/MDS
- ECOG performance status 0 – 3
- Adequate hepatic function as defined by bilirubin less than 1.5 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT)less than 2.5 x ULN
- Adequate renal function, with serum creatinine less than 1.5 x ULN
- Patients with no uncontrolled active infection
- Patient currently taking any investigational product or have received an investigational product within 28 days prior to screening.
- Hydroxyurea ceased 48 hours prior to study therapy
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any serious medical or psychiatric conditions which the investigator feels may interfere with the patient’s ability to give informed consent or participate in the procedures or evaluations of the study
- Severe peripheral blood thrombocytopenia (<10 x 10^9/L) resistant to correction by platelet transfusion when measured 24 hours later
- Severe peripheral blood hyperleukocytosis (>50 X 10^9/L blast cells)
- Abnormal coagulation not corrected by plasma infusion (APTT > ULN or INR> 1.2)
- History of cerebrovascular disease (stroke within the past 2 years, any history of intracranial haemorrhage)
- History of major non-compliance to medication
- Evidence of CNS leukemia
- Uncontrolled infection
- Uncontrolled viral infection with known HIV or Hepatitis type B or C
- Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that prevents the patient from absorbing or taking oral medication
- Any other concurrent severe and/or uncontrolled medical conditions (e.g. acute or chronic liver disease, infection, pulmonary disease) that in the opinion of the investigator could potentiate unacceptable safety risks or jeopardize compliance with the protocol
- Patients of childbearing potential that do not agree to use at least 2 effective contraceptive methods throughout the study and for 6 months following the date of last dose
- Female patient who are pregnant or lactating.
- Current history of drug or alcohol abuse (more than 4 standard drinks per day and/or abnormal liver function tests two time the upper limit of normal range values)

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 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Safety concerns
Date of first participant enrolment
Anticipated
15/10/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 284883 0
Commercial sector/Industry
Name [1] 284883 0
Senz Oncology Pty Ltd
Country [1] 284883 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Senz Oncology Pty Ltd
Address
714 Main Street,
Eltham
VIC 3095.
Country
Australia
Secondary sponsor category [1] 283762 0
None
Name [1] 283762 0
Address [1] 283762 0
Country [1] 283762 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286879 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 286879 0
Alfred Hospital
Commercial Road
Melbourne
Victoria 3004
Ethics committee country [1] 286879 0
Australia
Date submitted for ethics approval [1] 286879 0
19/05/2012
Approval date [1] 286879 0
30/07/2012
Ethics approval number [1] 286879 0

Summary
Brief summary
This is a 2-stage, Phase I/II (3 + 3 dose escalation with an expansion phase), open label, single centre study to determine the safety, tolerability and preliminary efficacy of escalating doses of the experimental drug VAL-1000. Enrolled patients will have a bone marrow aspirate to determine the baseline blast count and to collect samples for correlative laboratory studies by the Investigator. This study is open to Male and Female subjects aged 18 years of age or over with Acute Myeloid Leukaemia, Acute Lymphoblastic Leukemia (ALL) or high-risk Myelodysplastic Syndromes (MDS), who are unsuitable for treatment with standard chemotherapy regimens. Further details on the inclusion and exclusion criteria for this study can be found in the relevant section of this form. Trial details In this study, you will be assigned to receive an ascending dose of 100mg, 150mg, 200mg up to 250mg of VAL-1000 daily via oral administration for 12 months, with three patients enrolled in each of these cohorts (study groups). The maximum dose you will receive may vary depending on the safety, tolerability and efficacy of the earlier doses of oral VAL-1000. Patients experiencing a Dose Limiting Toxicity (DLT) or disease progression will be taken off the study; other patients will continue to be treated daily with 50mg oral twice a day (100mg/day) VAL-1000. Further details of this treatment can be found in the Description of intervention(s)/ exposure field in this form, and may be discussed further with your treating clinician.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33913 0
Dr Andrew Wei
Address 33913 0
The Alfred Hospital
55 Commercial Rd, Melbourne VIC 3004
Country 33913 0
Australia
Phone 33913 0
+61 3 90762000
Fax 33913 0
Email 33913 0
a.wei@alfred.org.au
Contact person for public queries
Name 17160 0
Ms Kathy Skoff
Address 17160 0
Senz Oncology Pty Ltd
714 Main Street,
Eltham
VIC 3095.
Country 17160 0
Australia
Phone 17160 0
+61 (0) 409 596 088
Fax 17160 0
Email 17160 0
kathy.karl@bigpond.com
Contact person for scientific queries
Name 8088 0
Dr Dr Andrew Wei
Address 8088 0
Monash University and Alfred Hospital
Commercial Road,
Melbourne
Vic 3004
Country 8088 0
Australia
Phone 8088 0
+61 (0)3 9076 3451
Fax 8088 0
+61 (0)3 9076 2298
Email 8088 0
a.wei@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study was withdrawn


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
6764Ethical approvalEthics approval letter   362235-(Uploaded-29-01-2020-10-03-07)-Study-related document.pdf



Results publications and other study-related documents

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