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

Haematological Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01080664
• Other study ID #: 27335
• Status: Terminated
• Phase: Phase 1
• First received: March 2, 2010
• Last updated: October 21, 2013
• Start date: December 2006
• Est. completion date: August 2011

Study information

• Verified date: October 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: EthikkommissionBelgium: Institutional Review BoardItaly: Ethics CommitteeGermany: Ethics CommissionUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 124
• Est. completion date: August 2011
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Haematological Malignancies
• Hematologic Neoplasms
• Neoplasms

Intervention

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
• 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.

Locations

Country	Name	City	State
Belgium	Haematologie UZ Gasthuisberg	Leuven
Belgium	Mont-Godinne University Hospital (UCL)	Yvoir
Germany	Universitatsklinik Frankfurt	Frankfurt am Main
Germany	Technische Universitat Munchen	Munchen
Germany	Medizinische Universitatsklinik	Ulm
Italy	Policlinico Sant'Orsola Malpighi	Bologna
Switzerland	Kantonsspital Basel	Basel
Switzerland	Hospitaux Universitaires	Geneva
Switzerland	Kantonsspital St Gallen	St Gallen
United States	CTRC at the UT Health Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Treatment-emergent adverse events (TEAE)	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.	minimum 21 days or 1 cycle	No