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

NCT ID: NCT01080664

Last Updated: 2013-10-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2011-08-31

Brief Summary

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.

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.

Conditions

Haematological Malignancies

Keywords

AS703569; Aurora Kinase Inhibitor; Haematological malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regimen 1

Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle

Group Type: EXPERIMENTAL

AS703569

Intervention Type: DRUG

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

Regimen 2

Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle

Group Type: EXPERIMENTAL

AS703569

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Aurora kinase inhibitor; Aurora kinase inhibitor

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Narmyn Rejeb, M.D.

Role: STUDY_DIRECTOR

Merck Serono S.A., Geneva

Locations

CTRC at the UT Health Science Center at San Antonio

San Antonio, Texas, United States

Haematologie UZ Gasthuisberg

Leuven, , Belgium

Mont-Godinne University Hospital (UCL)

Yvoir, , Belgium

Universitatsklinik Frankfurt

Frankfurt am Main, , Germany

Technische Universitat Munchen

München, , Germany

Medizinische Universitatsklinik

Ulm, , Germany

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Kantonsspital Basel

Basel, , Switzerland

Hospitaux Universitaires

Geneva, , Switzerland

Kantonsspital St Gallen

Sankt Gallen, , Switzerland

Countries

United States; Belgium; Germany; Italy; Switzerland

References

Graux C, Sonet A, Maertens J, Duyster J, Greiner J, Chalandon Y, Martinelli G, Hess D, Heim D, Giles FJ, Kelly KR, Gianella-Borradori A, Longerey B, Asatiani E, Rejeb N, Ottmann OG. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies. Leuk Res. 2013 Sep;37(9):1100-6. doi: 10.1016/j.leukres.2013.04.025. Epub 2013 Jun 5.

Reference Type: DERIVED

PMID: 23746966 (View on PubMed)

Other Identifiers

27335

Identifier Type: -

Identifier Source: org_study_id