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

NCT01080664 | Terminated Phase 1

• 1 other identifier: 27335
• Study Type: interventional
• Target: 124
• Locations: 5 countries
• Sites: 10

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.

Conditions

Haematological Malignancies

Keywords

AS703569; Aurora Kinase Inhibitor; Haematological malignancies

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT)

  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.

  21 days or 1 cycle

• Preliminary anti-tumour activity

  Cohort expansion part - Preliminary anti-tumour activity in four selected cohorts of haematological malignancies as assessed every two cycles

  42 days or 2 cycles

Secondary Outcomes (1)

• Treatment-emergent adverse events (TEAE)

  minimum 21 days or 1 cycle

Study Arms (2)

Regimen 1

EXPERIMENTAL

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

Drug: AS703569

Regimen 2

EXPERIMENTAL

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

Drug: AS703569

Interventions

AS703569 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

Also known as: Aurora kinase inhibitor

Regimen 1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (10)

CTRC at the UT Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Haematologie UZ Gasthuisberg

Leuven, 3000, Belgium

Location

Mont-Godinne University Hospital (UCL)

Yvoir, B-5530, Belgium

Location

Universitatsklinik Frankfurt

Frankfurt am Main, D-60590, Germany

Location

Technische Universitat Munchen

München, D-81675, Germany

Location

Medizinische Universitatsklinik

Ulm, D-89070, Germany

Location

Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Kantonsspital Basel

Basel, CH-4031, Switzerland

Location

Hospitaux Universitaires

Geneva, 1211, Switzerland

Location

Kantonsspital St Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 23746966 DERIVED

MeSH Terms

Interventions

MSC1992371A

Study Officials

• Narmyn Rejeb, M.D.

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2010
• First Posted: March 4, 2010
• Study Start: December 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: August 1, 2011
• Last Updated: October 22, 2013

Record last verified: 2013-10

Locations

IT (1); BE (2); US (1); CH (3); DE (3)