Volasertib in Combination With Azacitidine in Japanese Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

NCT02201329 | Completed Phase 1 Results

• 1 other identifier: 1230.35
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

To identify the maximum tolerated dose or recommended dose for further development of volasertib in combination with azacitidine in Japanese patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, and evaluate the safety and tolerability, pharmacokinetics and the preliminary efficacy of this combination.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

  This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLT was defined as any of the following Adverse Events (AEs) considered to be related to the study drug (Volasertib and/or Azacitidine). 1. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 drug-related non-haematologic toxicity. 2. Drug-related AEs that led to inability to deliver the full dose of the study drugs (Volasertib and/or Azacitidine) according to the assigned dose level within Cycle 1. 3. Absence of haematological recovery (sustained CTCAE grade ≥3 thrombocytopenia \<50000/mm\^3 and/or neutropenia \<1000/mm\^3) after completing Cycle 1 and lasting at least until Day 57 (from Day 1 of Cycle 1) despite complete marrow blast clearance on Day 29 (\<5% blasts in the bone marrow. 4. Any other drug-related AEs that required treatment delay of ≥4 weeks between the Cycle 1 and Cycle 2 (i.e., Cycle 2 was not started until Day 57 of Cycle 1)).

  Up to 57 days.

• Maximum Tolerated Dose of Volasertib

  This outcome measure presents MTD of Volasertib in Combination with Azacitidine. The MTD was defined as the highest dose level at which Dose Limiting Toxicities (DLTs) were reported in not more than 1 in 6 evaluable patients during Cycle 1.

  Up to 57 days.

Secondary Outcomes (3)

• Overall Objective Response (OR): Complete Remission (CR), Partial Remission (PR), or Marrow CR (mCR)

  Up to 9 months.

• Maximum Measured Concentration of the Volasertib 200 mg in Plasma (Cmax)

  -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.

• Area Under the Concentration-Time Curve of Volasertib 200 mg in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

  -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.

Study Arms (1)

A

EXPERIMENTAL

Volasertib escalating doses + azacitidine

Drug: Azacitidine; Drug: Volasertib

Interventions

Azacitidine DRUG

Azacitidine (subcutaneous)

A

Volasertib DRUG

Volasertib escalating doses (intravenous)

A

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of age \>=20 and \<=80 years
• Patients with primary or treatment-related myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), who are not eligible for hematopoietic stem cell transplantation based on the investigator's judgment, that meet one of the following criteria:
• Intermediate-2 and high-risk MDS according to the International Prognostic Scoring System, in the setting of 5-30% bone marrow blasts
• CMML with \>= 10% marrow blasts without myeloproliferative disorder (white blood cell count of \<13,000/ µL)
• Patients with no prior azacitidine treatment, or with prior azacitidine treatment that meet one of the following criteria:
• Patients failing to achieve haematological improvement, partial remission, marrow complete remission or complete remission after 3 cycles of azacitidine or progressed at any time after start of azacitidine
• Patients achieved an initial response and subsequently develop disease progression or relapse
• Eastern Cooperative Oncology Group performance status score 0 or 1 at screening
• Signed written informed consent consistent with Good Clinical Practice.

You may not qualify if:

• Treatment with systemic therapy for MDS, including an investigational drug, within 14 days before the first dose of study treatment, except for lenalidomide within 12 weeks before the first dose of study treatment, or lack of recovery from any acute toxicities pertinent to the prior systemic therapy.
• Prior treatment with volasertib
• Contraindications for azacitidine treatment according to the manufacturer's product information
• Known hypersensitivity to the trial drugs or its excipients
• Concomitant malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer)
• QTcF prolongation \>470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).
• Total bilirubin \>1.5 x upper limit of normal (ULN) not related to Gilbert's syndrome, hemolysis, or secondary to MDS at screening
• Aspartate amino transferase or alanine amino transferase \>2.5 x ULN
• Serum creatinine \>1.5 x ULN at screening
• Arterial oxygen pressure \<60 torr or arterial oxygen saturation \<92% (at room air)
• Active hepatitis B or hepatitis C, or laboratory evidence of hepatitis with positive results of hepatitis B surface antigen and/or hepatitis C antibody.
• Human immunodeficiency virus infection.
• Severe illness or organ dysfunction involving the heart, lung, kidney, liver or other organ system, which in the opinion of the investigator would interfere with the evaluation of the safety of the study treatment including; infection requiring active treatment, poorly controlled ventricular/atrial tachyarrhythmia, use of heart pacer, unstable angina pectoris, history of myocardial infarction or severe congestive heart failure, clinically unstable cardiac or pulmonary disease
• Any 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
• All male patients and female patients of child bearing potential who are unwilling to use a medically acceptable method of contraception during the trial and at least 6 months after the end of study treatment (i.e. hormonal contraception, intrauterine device, condom with spermicide, etc.). Note: females are considered to be of child bearing potential unless they have been surgically sterilized or are post-menopausal (complete absence of menses for at least 12 months without other medical reasons).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (4)

Boehringer Ingelheim Investigational Site

Aichi, Nagoya, Japan

Location

Boehringer Ingelheim Investigational Site

Gunma, Maebashi, Japan

Location

Boehringer Ingelheim Investigational Site

Nagasaki, Nagasaki, Japan

Location

Boehringer Ingelheim Investigational Site

Tokyo, Sinagawa-ku, Japan

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Azacitidine; BI 6727

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2014
• First Posted: July 28, 2014
• Study Start: August 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2017-10

Locations

JP (4)