Phase I/IIa Trial to Investigate BI 6727 (Volasertib) as Monotherapy or in Combination With Cytarabine in Acute Myeloid Leukaemia
Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I: Maximum Tolerated Dose (MTD) of Volasertib in Combination With LDAC (Schedule A) and Volasertib Monotherapy (Schedule B) |
350; 450 | — |
| PRIMARY Phase II: Number of Patients With Objective Response (Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi)) |
6; 13 | 0.0523 |
| PRIMARY Phase I: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) |
0; 0; 0; 1; 1; 2 | — |
| SECONDARY Best Overall Response |
0; 0; 2; 0; 0; 0 | — |
| SECONDARY Phase I: Number of Patients With Objective Response: Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR+CRi) |
0; 2; 2; 1; 1; 0 | — |
| SECONDARY Phase II: Event Free Survival |
69.0; 169.0 | 0.0208 sig |
| SECONDARY Phase II: Overall Survival |
158.0; 245.0 | 0.0465 sig |
| SECONDARY Phase II: Relapse - Free Survival |
304.0; 563.0 | — |
| SECONDARY Phase II: Remission Duration |
367.0; 687.0 | — |
| SECONDARY Phase II: Time to Remission |
63.5; 71.0 | — |
| SECONDARY Best Eastern Co-operative Oncology Group (ECOG) Performance Score From Baseline Until End of Treatment |
3; 1; 5; 2; 5; 1 | — |
| SECONDARY Total Clearance (CL) of Volasertib in Plasma After i.v (Intravenous) Administration of Volasertib |
1280; 972; 864; 1150; 1000; 852 | — |
| SECONDARY Apparent Volume of Distribution of Volasertib at Steady State (VSS) |
10600; 8640; 7000; 6320; 5270; 4830 | — |
| SECONDARY Dose Normalized Maximum Measured Concentration of Cytarabine in Plasma (Cmax, Norm) |
2.92; 2.83; 2.36 | — |
| SECONDARY Dose Normalized Area Under the Concentration-Time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated up to 4 Hours |
3.84; 4.00; 3.94 | — |
| SECONDARY Absolute QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Intervals |
411.6; 412.4; 430.0; 441.1; 414.0; 411.9 | — |
| SECONDARY QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Change From Baseline at Cycle 1 |
18.5; 29.6; 1.9; -0.5 | — |
| SECONDARY Phase I Schedule A: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During Cycle 1 |
0; 0; 1; 1; 2; 1 | — |
| SECONDARY Phase I Schedule B: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During Cycle 1 |
5; 0; 1; 0; 5; 0 | — |
| SECONDARY Phase I Schedule A: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles |
1; 0; 0; 1; 2; 1 | — |
| SECONDARY Phase I Schedule B: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles |
5; 0; 1; 0; 3; 0 | — |
| SECONDARY Phase II: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles |
13; 12; 13; 20; 6; 8 | — |
Eligibility Criteria
Inclusion criteria
Male or female adult with relapsed/refractory AML ineligible for intensive treatment (phase I part only) Male or female adult with previously untreated AML ineligible for intensive treatment (phase IIa part only) Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL) Patient is eligible for LD-Ara-C treatment Life expectancy > 3 months Eastern co-operative oncology group (ECOG, R01-0787) performance score 470 ms) Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN in case of known leukaemia liver involvement Prothrombin time (PT) > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin) Bilirubin greater than 1.5 mg/dl (> 26 mcmol/L) Serum creatinine greater than 2.0 mg/dl Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris, cardiac arrhythmia or severe heart failure/cardiac insufficiency.
Psychiatric illness or social situation that would limit compliance with trial requirements Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug Contraindications for cytarabine treatment according to the SPC Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial, i.e. combination of two forms of effective contraception (hormonal contraception, intrauterine device, condom with spermicide, etc.).
Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial Pregnant or nursing female patients Patient unable to comply with the protocol
Data sourced from ClinicalTrials.gov (NCT00804856). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.