An exploratory Phase I/II Clinical Evaluation of VAL-1000 in adults with Acute Leukaemias
An exploratory Phase I/II safety and tolerability clinical evaluation of VAL-1000 in adults with Acute Leukaemias
Senz Oncology Pty Ltd
24 participants
Oct 15, 2012
Interventional
Conditions
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.
Eligibility
Inclusion Criteria10
- 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 Criteria14
- 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)
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Interventions
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.
Locations(1)
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ACTRN12612000970842