Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia PXD101 Belinostat Idarubicin
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 41
Healthy volunteers: no

Brief summary:
An open-label, non-randomized, multi-centre, Phase I/II trial to assess the efficacy and safety of 2 schedules of PXD101 in combination with idarubicin in patients with AML not suitable for standard intensive therapy.

Detailed description:
This trial is an open-label, multi-centre, dose-escalation Phase I/II study to evaluate safety, explore efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with idarubicin administered in two different schedules in patients with AML. The PXD101 plus idarubicin treatment will be repeated at suitable intervals (target is every 3 weeks for schedule A and every 2 weeks for schedule B) depending upon toxicities or disease progression. Safety and efficacy assessments will be performed at every cycle.

Schedule A uses PXD101 by 30 min infusion daily for 5 days every 3 weeks with escalating doses of idarubicin.

Schedule B uses escalating doses of continuous infusion (48h) of PXD101 alone or in combination with idarubicin.

In both regimens the trial may be expanded at the Maximum Tolerated Dose (MTD).

Arms:
arm 1: PXD101 administered as a 30-minute intravenous (IV) infusion of 1000 mg/m²/d for five consecutive days every 3 weeks.

Idarubicin administered on day 5 (first steps) or days 4 and 5 (later steps). Patients will be treated in a 21-day cycle for a minimum of 2 cycles and a maximum of 6 cycles (depending on cumulated idarubicin dose). arm 2: PXD101 administered by continuous intravenous infusion over 24-48 hours and idarubicin (in the later steps) added after the first 24 hours. The second cycle will start on day 15 but under observation of possible toxicity. Further cycles will be administered q 14 d for up to 6 cycles. The first dose steps will be carried out with PXD101 alone for safety reasons.

Interventions: intervention 1: PXD101 intervention 2: idarubicin
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: