Phase I Dose Escalation Trial of Volasertib in Combination With Azacitidine in Patients With MDS or CMML

Phase 1

Terminated

Brief Summary: 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

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Schedule A	Azacitidine	Volasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule B	Azacitidine	Volasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule C	Volasertib	Volasertib (d 1 and 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule C	Azacitidine	Volasertib (d 1 and 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule B	Volasertib	Volasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule A	Volasertib	Volasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)

Primary Outcome Measures

Name	Time	Method
Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1	4 weeks	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.
Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1	4 weeks	Number of participants with Dose Limiting Toxicities (DLT) in Cycle 1 (escalation part to determine MTD) is presented .

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With Objective Response (OR)	From randomisation until data cut-off (16Dec2016); up to 159 weeks	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

Locations (14): 1230.33.33002 Boehringer Ingelheim Investigational Site
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Marseille, France
1230.33.33001 Boehringer Ingelheim Investigational Site
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Paris, France
1230.33.49002 Boehringer Ingelheim Investigational Site
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Dresden, Germany
1230.33.49011 Boehringer Ingelheim Investigational Site
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Berlin, Germany
1230.33.49008 Boehringer Ingelheim Investigational Site
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Hannover, Germany
1230.33.49012 Boehringer Ingelheim Investigational Site
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Kassel, Germany
1230.33.49014 Boehringer Ingelheim Investigational Site
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Leipzig, Germany
1230.33.49001 Boehringer Ingelheim Investigational Site
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Düsseldorf, Germany
1230.33.49005 Boehringer Ingelheim Investigational Site
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Frankfurt/Main, Germany
1230.33.49004 Boehringer Ingelheim Investigational Site
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Freiburg, Germany
1230.33.49009 Boehringer Ingelheim Investigational Site
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Mannheim, Germany
1230.33.49003 Boehringer Ingelheim Investigational Site
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Ulm, Germany
1230.33.49010 Boehringer Ingelheim Investigational Site
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Hamburg, Germany
1230.33.49006 Boehringer Ingelheim Investigational Site
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München, Germany