An exploratory Phase I/II Clinical Evaluation of VAL-1000 in adults with Acute Leukaemias

Phase 1

Withdrawn

• Conditions: Acute Leukaemias; Cancer - Leukaemia - Acute leukaemia

• Registration Number: ACTRN12612000970842
• Lead Sponsor: Senz Oncology Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-09-10
• Last Update Posted: 10 February 2020

Recruitment & Eligibility

• Status: Withdrawn
• Sex: All
• Target Recruitment: 24

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

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

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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:<br>- 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.<br>-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).<br>-Adverse events will be summarised by worst NCI CTC V4 grade.<br>-Laboratory data will be graded according to NCI CTC V4 severity grade[At the end of study]

Secondary Outcome Measures

Name	Time	Method
Patient related efficacy outcomes this will be done by the Principal Investigator using the following criteria:<br>-Assesing response ,PR/CR/CRi according to Cheson criteria (Cheson et al., 2003) in patients receiving at least 1 cycle (4 weeks) of treatment<br>-Progression-free survival (PFS)<br>-Overall survival (OS) <br>-Time to complete remission[At the end of study];To define a dose level for testing in subsequent phase II clinical trials. This will be done by cclinical assesment and adverse event profile.[At the end of study];To assess drug pharmacokinetics this will be done by blood analysis.[At the end of study]