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Volasertib in Combination With Azacitidine in Japanese Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Phase 1
Completed
Conditions
Myelodysplastic Syndromes
Leukemia, Myelomonocytic, Chronic
Interventions
Registration Number
NCT02201329
Lead Sponsor
Boehringer Ingelheim
Brief Summary

To identify the maximum tolerated dose or recommended dose for further development of volasertib in combination with azacitidine in Japanese patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, and evaluate the safety and tolerability, pharmacokinetics and the preliminary efficacy of this combination.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
5
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AAzacitidineVolasertib escalating doses + azacitidine
AVolasertibVolasertib escalating doses + azacitidine
Primary Outcome Measures
NameTimeMethod
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)Up to 57 days.

This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLT was defined as any of the following Adverse Events (AEs) considered to be related to the study drug (Volasertib and/or Azacitidine).

1. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 drug-related non-haematologic toxicity.

2. Drug-related AEs that led to inability to deliver the full dose of the study drugs (Volasertib and/or Azacitidine) according to the assigned dose level within Cycle 1.

3. Absence of haematological recovery (sustained CTCAE grade ≥3 thrombocytopenia \<50000/mm\^3 and/or neutropenia \<1000/mm\^3) after completing Cycle 1 and lasting at least until Day 57 (from Day 1 of Cycle 1) despite complete marrow blast clearance on Day 29 (\<5% blasts in the bone marrow.

4. Any other drug-related AEs that required treatment delay of ≥4 weeks between the Cycle 1 and Cycle 2 (i.e., Cycle 2 was not started until Day 57 of Cycle 1)).

Maximum Tolerated Dose of VolasertibUp to 57 days.

This outcome measure presents MTD of Volasertib in Combination with Azacitidine. The MTD was defined as the highest dose level at which Dose Limiting Toxicities (DLTs) were reported in not more than 1 in 6 evaluable patients during Cycle 1.

Secondary Outcome Measures
NameTimeMethod
Overall Objective Response (OR): Complete Remission (CR), Partial Remission (PR), or Marrow CR (mCR)Up to 9 months.

This outcome measure presents overall Objective Response (CR+PR+mCR). Response to treatment was evaluated according to the International Working Group (IWG) 2006 criteria. Best response was tabulated from all available data, with each patient being classified into one of the categories defined in CR, PR, mCR.

Maximum Measured Concentration of the Volasertib 200 mg in Plasma (Cmax)-0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.

This outcome measure presents maximum measured concentration of Volasertib 200 mg in plasma (Cmax).

Area Under the Concentration-Time Curve of Volasertib 200 mg in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)-0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.

This outcome measure presents area under the concentration-time curve of Volasertib 200 mg + Azacitidine 75 mg/m\^2 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).

Trial Locations

Locations (1)

Boehringer Ingelheim Investigational Site

🇯🇵

Tokyo, Sinagawa-ku, Japan

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