Trial Identifiers
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Scientific Title
A Phase I, Open Label Dose Escalation Trial of Orally Administered N-methyl-pyrrolidone (NMP) in Patients With Relapsed or Refractory Myeloma
Other Non-Commercial Sponsor
Peter MacCallum Cancer Centre
Summary
The study will evaluate if the N-methyl-pyrrolidone (NMP) can be safely administered to humans at doses, which induce measurable immunological and anti-tumour effects in patients with myeloma who are resistant to or intolerant of lenalidomide and bortezomib.
Nâ€Methylâ€2â€pyrrolidone (NMP) is a small molecule acetylâ€lysine mimetic compound with potent (low micromolar range) immunomodulatory and direct antiâ€myeloma activity attributable to BETbromodomain inhibition at higher concentrations. NMP is nontoxic, stable and already in use as a solvent in biomedical applications. It has been the subject of numerous toxicity studies in humans and been demonstrated to have few adverse effects. The study is proposing an empiric starting dose of 50mg daily, 50% of that seen in healthy volunteers with no observable toxicity. Dose escalation will follow a rule based on accelerated trial design in order to minimise the number of patients treated at subâ€therapeutic doses and minimise the length of the study. During the accelerated doseâ€escalation phase, one patient will be entered per cohort with a dose escalation increment of 100%, with up to 6 dose escalation and up to two dose deâ€escalation levels.The accelerated phase ends when one patient experiences DLT during the first cycle of treatment or when a total of two patients have experienced moderate toxicity during the first cycle of treatment regardless of the dose level; or the most recent patient has been treated at the highest dose level in the first cycle. If 1 patient experiences a DLT in the first cycle at any dose level, the cohort will be further expanded to a total of 6 patients treated at the same dose level. The maximum tolerated dose (MTD) in the study will be defined as the highest dose in which the incidence of DLT was less than 33%.