NCT01957644 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2019-02-08

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1

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outcome · POSTED

Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1

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outcome · POSTED

Percentage of Patients With Objective Response (OR)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion criteria: * Adult patients with previously untreated, intermediate-2 or high- risk MDS or CMML not eligible for hematopoietic stem cell transplantation (HSCT) based on documented patients characteristics like age, performance status, concomitant diagnoses, and organ dysfunctions * Further inclusion criteria apply Exclusion criteria: * Prior or concomitant therapy for higher risk MDS (for example, but not limited to, hypomethylating agents like azacitidine). Note: Prior treatment with erythropoetin (EPO) is allowed up to \> 1 week before treatment with study medication. Patients must have not received MDS therapy since diagnosis of higher-risk MDS. However, previous lenalidomide treatment could have been administered for lower-risk MDS treatment as long as this therapy was discontinued at least \> 4 weeks before initiation of the current study treatment. * Treatment with any investigational drug within 2 weeks before first administration of present trial drug or within less than 5 half lives of the investigational drug before treatment with the present trial drug, whichever is longer. * Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer). * Corrected QT interval according to Fridericia (QTcF) prolongation \> 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).The QTcF will be calculated as the mean of the 3 Electrocardiograms (ECGs) taken at screening. * Total bilirubin \> 1.5 x upper limit of normal not related to Gilberts disease, hemolysis, or secondary to MDS. * Aspartate amino transferase (AST) or alanine amino transferase (ALT) \> 2.5 x the upper limit of normal (ULN) Creatinine \> 1.5 x ULN * Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection (hepatitis test results done in routine diagnostics are acceptable if done within 14 days before first study treatment dose). * HIV infection (HIV test results in routine diagnostics are acceptable if done within 14 days before first study treatment dose). * Severe illness or organ dysfunction involving the kidney, liver or other organ system (e.g. active uncontrolled infection , unstable angina pectoris or history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease), which in the opinion of the investigator would interfere with the evaluation of the safety of the study treatment * Further exclusion criteria apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Volasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
intervention Names
Drug: Azacitidine
Drug: Volasertib
label
Schedule A
type
EXPERIMENTAL
description
Volasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
intervention Names
Drug: Azacitidine
Drug: Volasertib
label
Schedule B
type
EXPERIMENTAL
description
Volasertib (d 1 and 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
intervention Names
Drug: Azacitidine
Drug: Volasertib
label
Schedule C
type
EXPERIMENTAL

interventions

arm Group Labels
Schedule A
Schedule B
Schedule C
name
Azacitidine
type
DRUG
arm Group Labels
Schedule A
Schedule B
Schedule C
name
Volasertib
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 16
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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

secondary Outcomes

description
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
measure
Percentage of Patients With Objective Response (OR)
time Frame
From randomisation until data cut-off (16Dec2016); up to 159 weeks

Full study description

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

Source references