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

Boehringer Ingelheim

Status and phase: Terminated; Phase 1

Conditions: Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Treatments: Drug: Volasertib; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01957644

2013-001290-24 (EudraCT Number)

1230.33

Details and patient eligibility

About

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

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

Schedule A

Experimental group

Description:

Volasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)

Treatment:

Drug: Azacitidine

Drug: Volasertib

Schedule B

Experimental group

Description:

Volasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)

Treatment:

Drug: Azacitidine

Drug: Volasertib

Schedule C

Experimental group

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)

Treatment:

Drug: Azacitidine

Drug: Volasertib