Combined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorClinical Hub for Interventional Research (CHOIR)
About this trial
The goal of this project is to see if two new potential treatments (defactinib and the combination tablet of decitabine/cedazuridine) can safely be combined to improve outcomes in people with high-risk myelodysplastic syndrome (MDS), certain forms of Acute Myeloid Leukaemia (AML), and Chronic Myelomonocytic Leukaemia (CMML). Decitabine/cedazuridine is approved for use by the Australian Therapeutics Goods Administration (TGA) as treatment for MDS. Defactinib is an experimental treatment. This means it is not an approved treatment for MDS in Australia. So far it has been given to over 625 patients in studies across the world.
All study participants will receive active treatment, there is no placebo. Participants will take the decitabine/cedazuridine treatment once a day for 5 days in a row (day 1 to day 5) on its own for the first month (cycle). From month 2 participants will take the decitabine/cedazuridine treatment and will also take the defactinib treatment, both for 5 days in a row on days 1 to day 5 each month (cycle). Defactinib is taken twice a day.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years
Myelodysplastic syndrome (MDS) classified as intermediate-2 or high risk according to the International Prognostic Scoring System (IPSS), or
Acute Myeloid Leukaemia (AML) with 20-30% marrow blasts and multilineage dysplasia, according to WHO classification, or
Chronic myelomonocytic leukemia (CMML) with 10-29% marrow blasts without myeloproliferative disorder according to World Health Organisation (WHO) classification. This confirmation will be from either the Bone marrow aspirate (BMA) performed at screening or a standard of care BMA if performed up to 6 weeks before cycle 1 day 1.
Disqualifiers
Acute myeloid leukemia (AML) with ≥ 30% blasts in bone marrow according to WHO classification.
Prior allogeneic or autologous stem cell transplant.
Prior receipt of >1 cycle of a hypomethylating agent.
Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
Trial design
Design model
Single group
Treatments tested in this trial
Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLET
DrugFixed dose treatment cycles 1 to 6. Cycle 1 is monotherapy, cycles 2 to 6 combination therapy with defactinib.
Defactinib
DrugDefactinib treatment will commence with at the starting dose (dose level 1) from cycle 2 to 6. Dose escalation/de-escalation will proceed based on the MTD determination. Dose Level 1: 200mg Defactinib twice daily (starting dose level) Dose Level 2: 400mg defactinib twice daily Dose Level -1: 200mg Defactinib daily
Treatment groups
12 Participants
are divided into 1 treatment groupGroup A: Decitabine/cedazuridine + defactinibExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Maximum tolerated dose
Maximum dose at which no more than 1 of 6 participants experience a dose limiting toxicity (DLT)
Time frame
Once 3 participants have completed 2 cycles, assessed at approximately 2 months (each cycle is 28 days)Secondary outcomes
1
Number of Grade 3 or 4 adverse events
Number of participants experiencing Grade 3 or 4 adverse events or serious adverse events (SAEs) during cycles 1-6, along with description of events
Time frame
End of cycle 6 (24 weeks, each cycle is 28 days)2
Proportion of Grade 3 or 4 adverse events
Proportion of participants experiencing Grade 3 or 4 adverse events or serious adverse events (SAEs) during cycles 1-6, along with description of events
Time frame
End of cycle 6 (24 weeks, each cycle is 28 days)3
Number of participants completing planned therapy
Number of participants completing the planned six cycles of therapy, along with description of cycle delays
Time frame
End of cycle 6 (24 weeks, each cycle is 28 days)4
Proportion of participants completing planned therapy
Proportion of participants completing the planned six cycles of therapy, along with description of cycle delays
Time frame
End of cycle 6 (24 weeks, each cycle is 28 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Clinical Hub for Interventional Research (CHOIR)
Lead sponsor
The University of New South Wales
Collaborator
Australian National University
Collaborator
Source ClinicalTrials.gov