Trial of Volasertib With or Without Azacitidine in Patients With Myelodysplastic Syndromes

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02721875
• Date of registration: 23/03/2016
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim
• Public title: Trial of Volasertib With or Without Azacitidine in Patients With Myelodysplastic Syndromes
• Scientific title: An Open Label, Phase I Trial of Intravenous Administration of Volasertib as Monotherapy and in Combination With Azacitidine in Patients With Myelodysplastic Syndrome After Hypomethylating Agents Treatment Failure
• Date of first enrolment: April 28, 2016
• Target sample size: 1
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02721875
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada, France, Japan, Singapore, Spain, Taiwan, United States

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion criteria

Inclusion criteria:

- Patients 18 years and older with diagnosis of WHO classification-defined primary or
treatment-related myeloid neoplasms classified as follows:

- Refractory anaemia with excess blasts (RAEB)-1 (5%-9% marrow blasts) or

- RAEB-2 (10%-19% marrow blasts or 5% - 19% peripheral blast) or

- Chronic Myelomonocytic Leukaemia (CMML) (5%-19% blasts) with white blood cell (WBC)
count <13000/mm3 or

- Acute Myeloid Leukaemia (AML) (20%-29% marrow blasts, i.e., RAEB-t according to
French-American-British [FAB] classification) with WBC count <10000/mm3

- Patients classified as intermediate, high or very high-risk according to Revised -
International Prognostic Scoring System (IPSS-R) at the time of enrolment

- Patients who have received a maximum of 24 cycles of frontline HMA treatment prior to
enrolment.

- Patients must have received a minimum prior dosing schedule of either:

- Azacitidine 75 mg/m2 x 5 days per cycle or 50 mg/m2 x 7 days per cycle, or

- Decitabine 20 mg/m2 x 5 days per cycle, or

- SGI-110 60 mg/m2 x 5 days per cycle

- Patients must meet either one of the following criteria:

- Progressive disease (PD, according to 2006 International Working Group (IWG) criteria)
at any time after initiation of the prior HMA treatment, or

- Relapse after initial complete (CR) or partial remission (PR) or haematological
improvement (HI) (according to 2006 IWG criteria); or

- Failure to achieve complete or partial remission or HI (according to 2006 IWG) with no
evidence of progression (i.e., Stable Disease [SD]) after at least six cycles of prior
azacitidine treatment or at least four cycles of other prior HMA treatment.

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 at screening

- Signed written informed consent consistent with International Conference of
Harmonization Good Clinical Practice (ICH-GCP) and local legislation

Exclusion criteria:

- Prior systemic therapy (including investigational drugs) for MDS, CMML or AML within
14 days before treatment with study medication.

- Patients requiring intervention for white blood cell count control with hydroxyurea,
chemotherapy, or leukapheresis.

- Prior exposure to more than one line of HMA based treatment.

- Prior exposure to volasertib or other polo-kinase inhibitors

- Patients who were unable to tolerate prior HMA treatment

- Patients with history of hematopoietic stem cell transplant (HSCT)

- Known hypersensitivity to the trial drugs or its excipients

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

- QTcF value >470 ms or QT prolongation deemed clinically relevant by the investigator
(e.g., congenital long QT syndrome).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Myelodysplastic Syndromes

Intervention(s)

Drug: Azacitidine

Drug: Volasertib

Primary Outcome(s)

Maximum Tolerated Dose (MTD) of Volasertib [Time Frame: First treatment cycle, up to 28 days]

Number of Patients With Dose Limiting Toxicities (DLT) in the First Cycle [Time Frame: First treatment cycle, up to 28 days]

Secondary Outcome(s)

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Measured Time Point tz of Volasertib (AUC0-tz) (for Monotherapy) [Time Frame: Pharmacokinetic (PK) samples were taken at 5 minutes before drug administration and 0:30, 1:00, 2:00, 3:00, 4:00, 24:00, 167:55, 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after drug administration]

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity of Volasertib (AUC0-8) (for Combination) [Time Frame: PK samples were to be taken at 5 minutes before drug administration (167:55) and 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after first drug administration of Azacitidine]

Objective Response Defined as Best Overall Response of Complete Remission, Partial Remission or Haematological Improvement According to the International Working Group 2006 Criteria [Time Frame: Up to 168 days]

Maximum Measured Plasma Concentration of Volasertib (Cmax) (for Combination) [Time Frame: PK samples were to be taken at 5 minutes before drug administration (167:55) and 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after first drug administration of Azacitidine]

Maximum Measured Plasma Concentration of Volasertib (Cmax) (for Monotherapy) [Time Frame: PK samples were taken at 5 minutes before drug administration and 0:30, 1:00, 2:00, 3:00, 4:00, 24:00, 167:55, 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after drug administration]

Secondary ID(s)

2015-004490-32

1230.43

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/08/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02721875