Volasertib + Decitabine in Patients With Acute Myeloid Leukemia (AML)

Leukemia, Myeloid, Acute Clinical Trial

Official title:

An Open Label, Phase I, Dose Escalation Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics, and Efficacy of Volasertib in Combination With Decitabine in Patients >= 65 Years With Acute Myeloid Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02003573
• Other study ID #: 1230.30
• Secondary ID: 2013-001752-36
• Status: Terminated
• Phase: Phase 1
• Start date: January 29, 2014
• Est. completion date: May 15, 2016

Study information

• Verified date: August 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Dose Escalation (MTD Finding) Phase: To investigate the maximum tolerated dose (MTD), safety and pharmacokinetics of different volasertib administration schedules in combination with decitabine in previously untreated AML patients >= 65 years of age who are considered ineligible for standard intensive therapy, or patients with relapsed or refractory AML regardless of prior treatment status.

MTD Extension Phase: To collect additional data on safety, efficacy and pharmacokinetics of volasertib in combination with decitabine in previously untreated patients with AML >= 65 years of age and considered ineligible for standard intensive therapy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: May 15, 2016
• Est. primary completion date: January 6, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion criteria:

1. Dose Escalation Phase: patients with previously untreated AML, relapsed or refractory AML regardless of prior treatment status.

2. MTD Extension Phase: previously untreated AML (prior treatment for Myelodysplastic Syndrome(MDS) is allowed).

3. Age >= 65 years.

4. Previously untreated patients must be ineligible for receiving standard intensive therapy at the time of enrolment, in the opinion of the investigator and based on documented medical reasons.

5. Histologically or cytologically confirmed AML (except for APL, FAB (French-American-British)subtype M3) according to the World Health Organisation classification.

6. Eastern co-operative oncology group (ECOG) performance score =< 1 at screening.

7. Signed and dated written informed consent by start date of Screening Visit in accordance with Good Clinical Practice and local legislation.

Exclusion criteria:

1. MTD Extension Phase: Prior chemotherapy for AML (except for hydroxyurea). Patients can receive treatment with hydroxyurea in order to reduce high White Blood Cells count for no more than 28 days (cumulative); discontinuation of hydroxyurea at least one day prior to the study treatment is required. Please note that any prior therapy for MDS is allowed.

2. Acute promyelocytic leukemia (APL, FAB subtype M3), according to World Health Organisation classification.

3. Hypersensitivity to the trial drugs.

4. Other malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).

5. Known clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement.

6. QTcF (QT interval corrected for heart rate by the Fridericia formula) > 470 ms, calculated as the mean value of the triplicates taken at least 2 minutes apart at baseline or QTcF prolongation deemed clinically relevant by the investigator.

7. Baseline Left Ventricular Ejection Fraction of < 45% or below the lower limit of institutional normal range.

8. Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN). Patients with elevated liver enzyme(s) due to leukemic involvement are allowed up to = 5 x the ULN.

9. Total bilirubin > 1.5 x ULN. For patients with Gilbert's syndrome or elevation due to hepatic infiltrate, total bilirubin must be <4 x ULN.

10. Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation.

11. Severe illness or organ dysfunction involving the kidneys, liver or other organ system, including active uncontrolled infection, which in the opinion of the investigator precludes treatment with decitabine or would interfere with the evaluation of the safety of the study treatment.

12. Presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) Classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to study entry.

13. Significant concurrent psychiatric disorder or social situation that according to the investigator's judgment would compromise patient's safety or compliance, interfere with consent, study participation, or interpretation of study results.

14. Patients with a systemic fungal, bacterial, viral, or other infection that is not controlled.

15. Contraindications for decitabine treatment according to the manufacturer's prescribing information provided in the Investigator Site File

16. Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.

17. Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.

18. Pregnant or breast feeding patients.

19. Treatment with any investigational drug within 2 weeks of administration of first study medication dose or within less than five half -lives of the investigational drug before treatment with the present trial drug, whichever is shorter, and / or persistence of toxicities of prior anti-leukemic therapies which are deemed clinically relevant.

20. Prior treatment with a Plk inhibitor such as volasertib or treatment in a clinical trial using a Plk inhibitory compound.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• decitabine iv
decitabine iv fixed dose
• volasertib iv infusion
volasertib iv infusion (Body Surface Area (BSA) based dosing)

Locations

Country	Name	City	State
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	Washington School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 decitabine. 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 decitabine at which the incidence of DLT was =17% (i.e. 1/6 patients) during Cycle 1.	4 weeks
Primary	Number of Subjects With Dose Limiting Toxicities (DLT) in Cycle 1	Number of subjects with Dose Limiting Toxicities (DLT) in Cycle 1 is presented	4 weeks

External Links

•   Link