To investigate the maximum tolerated dose (MTD), safety, pharmacokinetics, and efficacy of volasertib in combination with azacitidine in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) and not candidates for hematopoietic stem cell transplant
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
1230.33.33002 Boehringer Ingelheim Investigational Site
Marseille, France
1230.33.33001 Boehringer Ingelheim Investigational Site
Paris, France
Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1
The primary objective of the dose-escalation part of this study was to determine the MTD of volasertib in combination with azacitidine. The MTD was to be identified based on the DLT information collected during the first treatment cycle of each dosing schedule. DLT was defined as a non-haematological drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3. The MTD corresponded to the highest dose of volasertib and azacitidine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1. The planned dose escalation schedules of Part 2 were not completed because the trial was prematurely discontinued. Hence, a final conclusion of the MTD of volasertib in combination with azacitidine cannot be drawn in this trial. Number of patients with DLT in cycle 1 in escalation part is presented to determine MTD.
Time frame: 4 weeks
Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1
Number of participants with Dose Limiting Toxicities (DLT) in Cycle 1 (escalation part to determine MTD) is presented .
Time frame: 4 weeks
Percentage of Patients With Objective Response (OR)
OR was defined as best overall response of complete remission (CR) or partial remission (PR) defined according to the International Working Group (IWG) 2006 criteria. Complete remission (CR): * Bone marrow: \<5 % myeloblasts with normal maturation of all cell lines\* * Persistent dysplasia will be noted\* * Peripheral blood: * hemoglobin (Hgb) \> 11 Grams Per Decilitre (g/dL) * Platelets \>100 x 109/L * Neutrophils \> 1.0 x 109/L * Blasts 0 % \*Dysplastic changes should consider the normal range of dysplastic changes Partial remission (PR): All CR criteria if abnormal before treatment except: * Bone marrow blasts decreased by \>50% to pre-treatment but still \>5% * Cellularity and morphology not relevant
Time frame: From randomisation until data cut-off (16Dec2016); up to 159 weeks
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1230.33.49011 Boehringer Ingelheim Investigational Site
Berlin, Germany
1230.33.49002 Boehringer Ingelheim Investigational Site
Dresden, Germany
1230.33.49001 Boehringer Ingelheim Investigational Site
Düsseldorf, Germany
1230.33.49005 Boehringer Ingelheim Investigational Site
Frankfurt am Main, Germany
1230.33.49004 Boehringer Ingelheim Investigational Site
Freiburg im Breisgau, Germany
1230.33.49010 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1230.33.49008 Boehringer Ingelheim Investigational Site
Hanover, Germany
1230.33.49012 Boehringer Ingelheim Investigational Site
Kassel, Germany
...and 4 more locations