Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Belinostat

Idarubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Histone Deacetylase Inhibitors

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).

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.

PXD101

idarubicin

e-mail contact via enquiries@topotarget.com

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.

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).

Trial of PXD101 (Belinostat) in Combination With Idarubicin to Treat AML Not Suitable for Standard Intensive Therapy

A Phase I/II Clinical Trial of PXD101 in Combination With Idarubicin in Patients With AML Not Suitable for Standard Intensive Therapy

DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle

Efficacy measured as Response rate (complete response (\[CR\] and Complete remission with incomplete recovery of platelets \[CRi\]) and partial response (\[PR\])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission).

Time to response: time in weeks from first treatment to obtainment of the particular response status (CR and PR)

Duration of Response (CR and PR) in Weeks

Overall survival: time in weeks from entry into study until death from any cause. All patients without this endpoint at the time of discontinuation or the end of trial have been censored.

Relapse-free survival: time (weeks) from leukemia-free state to relapse or death from any cause.

Event-free survival: time (weeks) from entry into study until treatment failure, disease relapse or death from any cause.

Remission duration: time (weeks) from date of remission status to disease relapse.

Cmax: Arm A: at Cycle 1 Day 4, Cycle 1 Day 5 Arm B: Cycle 1 Day 1 and Cycle 1 Day 2

Valerio Therapeutics

PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²

Arm A, Step 1

PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m²

Arm A, Step 2

PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d

Arm A, Step 3

PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d

Arm A, Step 4

PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours

Arm B, Steps 1-6

PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours

Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles

Arm B, Step 7

PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours

Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles

Arm B, Step 8

PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours

Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles

Arm B, Step 9

Total

Age, Categorical

Sex: Female, Male

PRS Admnistrator Gunilla Emanuelson

Maximum Tolerated Dose, Dose Limiting Toxicity

Overall Response

Time to response was reported among participants who reported response

Time to Response (CR and PR)

All patients who received at least one dose of belinostat and/or idarubicin were included in the full analysis set (FAS). Duration of response was reported among participants who reported response

Duration of Response (CR and PR)

Overall Survival

Relapse free survival was reported among participants who reported response

Relapse-Free Survival

Event-Free Survival

Remission duration was reported among participants who reported response

Remission Duration

Arm A, Cycle 1 Day 4

Arm A, Cycle 1 Day 5

Arm B, Cycle 1 Day 1 and Day 2

Results shown for dose level 1000 mg/m2/d

Belinostat Cmax

Belinostat AUC (Area Under Curve)

Elimination t½

PXD101 (belinostat) 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m²

Spots Global Cancer Trial Database for Trial of PXD101 (Belinostat) in Combination With Idarubicin to Treat AML Not Suitable for Standard Intensive Therapy

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial