A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies

This study has been terminated.
(Please see Purpose Statement below)
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01080664
First received: March 2, 2010
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

EMD Serono decided to terminate enrollment based on a review of the available clinical data and low probability of completing the trial based on the observed recruitment rate. Subjects already enrolled in the study continued participation in the study, consistent with the protocol, to study completion.


Condition Intervention Phase
Haematological Malignancies
Drug: AS703569
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Dose-Limiting Toxicity (DLT) [ Time Frame: 21 days or 1 cycle ] [ Designated as safety issue: No ]
    Dose-escalation part - The number of subjects experiencing at least a Dose-Limiting Toxicity (DLT), judged to be related to the study medication, evaluated over the first cycle only for each dose level and regimen, independently.

  • Preliminary anti-tumour activity [ Time Frame: 42 days or 2 cycles ] [ Designated as safety issue: No ]
    Cohort expansion part - Preliminary anti-tumour activity in four selected cohorts of haematological malignancies as assessed every two cycles


Secondary Outcome Measures:
  • Treatment-emergent adverse events (TEAE) [ Time Frame: minimum 21 days or 1 cycle ] [ Designated as safety issue: No ]
    Dose-escalation and Cohort expansion parts The proportion/number of subjects experiencing treatment-emergent adverse events (TEAE) after the first cycle and during multiple cycles, in each cohort for each of the 2 dose-regimens.


Enrollment: 124
Study Start Date: December 2006
Study Completion Date: August 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen 1
Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle
Drug: AS703569

Dose Escalation

Regimen 1 - 3-47 mg/m2/day, orally once daily on days 1, 2,3 and 8, 9, 10 of a 21 day cycle:

Number of cycles: until progression or unacceptable toxicity develops.

Cohort Expansion

Regimen 1 - Maximum tolerated dose from dose-escalation part or a lower dose in mg/m2/day, orally once daily on days 1, 2,3 and 8, 9, 10 of a 21 day cycle:

Number of cycles: until progression or unacceptable toxicity develops

Other Name: Aurora kinase inhibitor
Experimental: Regimen 2
Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle
Drug: AS703569

Dose Escalation Regimen 2 - 3-47 mg/m2/day, orally once daily on days 1, 2, 3, 4, 5, 6 of a 21 day cycle Number of cycles: until progression or unacceptable toxicity develops.

Cohort Expansion Regimen 2 - Maximum tolerated dose from dose-escalation part or a lower dose in mg/m2/day, orally once daily on days 1, 2, 3, 4, 5, 6 of a 21 day cycle Number of cycles: until progression or unacceptable toxicity develops.

Other Name: Aurora kinase inhibitor

Detailed Description:

The goal of this research study is to investigate for the first time the safety and tolerability of a new drug (AS703569), called an aurora kinase inhibitor, being tested to treat blood cancers in patients with different blood cancers. The research study will also assess how the body breaks down AS703569 and what changes occur in the blood after oral doses of AS703569. It will also look to see if there is any improvement in your blood cancer. The use of AS703569 in this study is experimental.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Dose-escalation part:

  • Primary or secondary acute myeloid leukaemia, including subjects:

with first or subsequent relapse after standard therapy, with no established treatment options; refractory to available therapies, e.g. who failed to achieve complete remission after chemotherapies; Newly-diagnosed elderly subjects (over 60 years) according to WHO classification (≥20 blasts in bone marrow), who did not accept or were not eligible for chemotherapy (first line therapy)

  • Subjects with myelodysplastic syndrome (IPSS Int-2 or high risk) resistant or intolerant to standard treatment and not candidates for allogeneic HSCT.
  • Subjects with chronic myeloid leukaemia in chronic, accelerated or blast-phase, resistant or intolerant to standard treatment and not candidates for allogeneic HSCT.
  • Subjects with myeloproliferative disorders and no effective treatment options.
  • Subjects with acute lymphoblastic leukaemia, relapsing, resistant or intolerant to standard treatment and no effective treatment options.
  • Subjects with chronic lymphocytic leukaemia, relapsing, resistant or intolerant to standard treatment and no effective treatment options.
  • Subjects with non-Hodgkin lymphoma, relapsing, resistant or intolerant to standard treatment with no effective treatment options.

Cohort expansion part

  • Primary or secondary acute myeloid leukaemia not eligible for chemotherapy (first line therapy), including subjects

with first or subsequent relapse after standard therapy, for whom no established treatment options are available; refractory to available therapies, e.g. who failed to achieve complete remission after chemotherapies; Newly-diagnosed elderly subjects (over 60 years) according to WHO classification (≥ 20 blasts in bone marrow), who did not accept or were not eligible for chemotherapy (first line therapy)

  • Subjects with chronic myeloid leukaemia in chronic or accelerated phase, resistant or intolerant to standard treatment, who have not achieved a complete haematological response, and are not candidates for allogeneic HSCT.
  • Subjects with myeloproliferative disorders with no effective treatment options.
  • Subjects with Philadelphia chromosome positive acute leukaemias including acute lymphoblastic leukaemia and blast phase chronic myeloid leukaemia, relapsing, resistant or intolerant to standard treatment with no effective treatment options.

Exclusion Criteria:

  • Acute promyelocytic leukaemia.
  • Ongoing uncontrolled bacterial, viral, fungal or atypical mycobacterial infection.
  • Hyperleukocytosis with >50x10(9)/L leukaemic blasts.
  • Chemotherapy, immunotherapy, biologic therapy or any experimental anti-cancer therapy within 28days prior to study Day1 and/or not having recovered from its toxicity.
  • Extensive radiotherapy involving ≥30% of bone marrow (e.g. whole pelvis, half spine) within 6months prior to study Day1.
  • Active CNS disease involvement.
  • Any condition, including laboratory, medical history or pre-study assessment findings, that in the opinion of the Investigator, constitute a risk or contraindication for participation or that could interfere with the study objectives, conduct or evaluation of a drug to be taken orally.
  • Clinically relevant cardiac abnormalities or clinically relevant abnormalities .
  • Known infection with human immunodeficiency virus, active hepatitis B, or hepatitis C.
  • Signs and symptoms suggestive of transmissible spongiform encephalopathy.
  • Major surgery within 2weeks prior to study Day1.
  • Haemoglobin <8g/dL at screening (can be transfused).
  • Refractory to platelet transfusion (defined as increase of <20.109/L platelets 1hour after transfusion).
  • Coexistent second malignancy or history of prior malignancy within previous 3years (excluding basal or squamous cell carcinoma of the skin, and in situ carcinoma of the cervix that has been treated curatively).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01080664

Locations
United States, Texas
CTRC at the UT Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Belgium
Haematologie UZ Gasthuisberg
Leuven, Belgium, 3000
Mont-Godinne University Hospital (UCL)
Yvoir, Belgium, B-5530
Germany
Universitatsklinik Frankfurt
Frankfurt am Main, Germany, D-60590
Technische Universitat Munchen
Munchen, Germany, D-81675
Medizinische Universitatsklinik
Ulm, Germany, D-89070
Italy
Policlinico Sant'Orsola Malpighi
Bologna, Italy, 40138
Switzerland
Kantonsspital Basel
Basel, Switzerland, CH-4031
Hospitaux Universitaires
Geneva, Switzerland, 1211
Kantonsspital St Gallen
St Gallen, Switzerland, 9007
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Narmyn Rejeb, M.D. Merck Serono S.A., Geneva
  More Information

No publications provided by EMD Serono

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01080664     History of Changes
Other Study ID Numbers: 27335
Study First Received: March 2, 2010
Last Updated: October 21, 2013
Health Authority: Switzerland: Ethikkommission
Belgium: Institutional Review Board
Italy: Ethics Committee
Germany: Ethics Commission
United States: Food and Drug Administration

Keywords provided by EMD Serono:
AS703569
Aurora Kinase Inhibitor
Haematological malignancies

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on April 17, 2014