Acute Myeloid Leukaemia MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Venclyxto
Product Name: Venclyxto
Pharmaceutical Form: Tablet
INN or Proposed INN: Venetoclax
CAS Number: 1257044-40-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concent
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of CD33 positive Acute Myeloid Leukaemia • Age =60 years (prior to the interim analyses performed after enrolment of 50 and 100 patients) • Genotype NPM1mut FLT3 ITDneg (FLT3- Tyrosine Kinase Domain mutation, TKD, is permitted) • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 • Serum creatinine = 1.5 x ULN (upper limit of normal) • Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) = 2.5 ULN and bilirubin = 2 x ULN • Able to provide written informed consent • Considered fit for intensive chemotherapy with anthracyclines by treating physician Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 46 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
Exclusion criteria: • Previous chemotherapy for AML or any antedecent haematological condition, with the exception of hydroxycarbamide to control white blood cell count • Other active malignancy requiring treatment • Newly diagnosed or uncontrolled HIV or hepatitis B or C infection. Patients with known chronic infections may enrol if the last two tests for viral load have been negative and their current therapy does not include a protease inhibitor or a non-nucleoside reverse-transcriptase inhibitor • Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) • Females of childbearing potential, and their partners, not willing to use adequate contraception during and for up to 6 months after treatment • Unable to swallow tablets whole
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Molecular event-free survival time (mEFS). An event is defined as follows: o Failure to achieve morphological CR or CRi after two cycles of therapy o Molecular persistence, progression or relapse requiring treatment change (at any time) o Morphological relapse (at any time) o Death (at any time);Timepoint(s) of evaluation of this end point: MEFS is calculated as the time from date of randomisation to the date of the first recorded event as stated above. Patients who have not experienced an event at the time of analysis will be censored at their date last seen without an event.;Main Objective: To compare molecular event free survival (mEFS) in AML patients receiving venetoclax and low dose cytarabine with those receiving intensive chemotherapy. mEFS is defined as; 1.Failure to achieve complete remission or complete remission with incomplete blood count recovery after two cycles of treatment 2.Molecular persistence (not responding to treatment), progression or relapse requiring treatment change 3.Morphological Relapse 4.Death;Secondary Objective: • Occurrence of complete remission by the end of the second cycle of treatment • Death within 30 and 60 days from trial entry • Overall survival time • Time to haematological relapse • Time to molecular relapse • Cumulative occurrence of grade 3 and 4 toxicity • Prevalence of molecular complete remission at month 3, 6 and 12 • Cumulative resource use at 12 and 24 months including hospital admission days, blood product usage and days on intravenous antibiotics and antifungals • Health related quality of life at month 3, 6, 12, 18 and 24 • Change in performance status from baseline at month 3, 6, 12, 18 and 24 • Change in Comprehensive Geriatric Assessment (CGA) from baseline at month 12 and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Occurrence of morphological complete remission (CR) by the end of the second cycle of treatment is evaluated from the morphological response assessments taken at the end of cycles 1 and 2. • Death within 30 and 60 days from trial entry will include deaths from any cause and can only be evaluated in those patients who have been followed up for these periods of time. • Overall survival time is calculated as time from date of randomisation to date of death from any cause; patients alive at the time of analysis will be censored at their date last seen alive. • Time to morphological relapse is calculated as the time from date complete morphological remission to date when morphological relapse is first recorded, where definition of morphological relapse and timings of assessments for morphological response are specified in protocol section 8.14. • Time to molecular relapse is calculated as the time from date of molecular remission to date when molecular relapse is first recorded, where definition of molecular relapse and timings of assessments for molecular response are specified in protocol section 8.14. • Cumulative occurrence of grade 3 and 4 adverse events (AE) at 12 and 24 months is evaluated as the total number of grade 3 and 4 AE that are reported during these periods, from all AE that are reported and graded according to CTCAE criteria throughout the duration of the trial. • Prevalence of molecular complete remission at month 3, 6 and 12 is evaluated from the molecular response assessments taken at these approximate time points from trial entry. • Cumulative resource use at 12 and 24 months is calculated as total number of hospital admission days, total blood product usage and total number of days on intravenous antibiotics and antifungals that are reported for these periods of time from trial entry. • Health-related quality of life (QoL) at month 3, 6, 12, 18 and 24 is evaluated from the EORTC QLQ-C30 and EQ-5D questionnaires completed | — |
Countries
Denmark, New Zealand, United Kingdom
Contacts
Public ContactLouise Hopkins
University of Birmingham
Outcome results
None listed