- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01080664
A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Leuven, Belgium, 3000
- Haematologie UZ Gasthuisberg
-
Yvoir, Belgium, B-5530
- Mont-Godinne University Hospital (UCL)
-
-
-
-
-
Frankfurt am Main, Germany, D-60590
- Universitätsklinik Frankfurt
-
Munchen, Germany, D-81675
- Technische Universität München
-
Ulm, Germany, D-89070
- Medizinische Universitätsklinik
-
-
-
-
-
Bologna, Italy, 40138
- Policlinico Sant'Orsola Malpighi
-
-
-
-
-
Basel, Switzerland, CH-4031
- Kantonsspital Basel
-
Geneva, Switzerland, 1211
- Hospitaux Universitaires
-
St Gallen, Switzerland, 9007
- Kantonsspital St Gallen
-
-
-
-
Texas
-
San Antonio, Texas, United States, 78229
- CTRC at The UT Health Science Center at San Antonio
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Regimen 1
Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle
|
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 Names:
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 Names:
|
Experimental: Regimen 2
Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle
|
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 Names:
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-Limiting Toxicity (DLT)
Time Frame: 21 days or 1 cycle
|
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
Time Frame: 42 days or 2 cycles
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-emergent adverse events (TEAE)
Time Frame: minimum 21 days or 1 cycle
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Narmyn Rejeb, M.D., Merck Serono S.A., Geneva
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 27335
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Haematological Malignancies
-
Ospedale Santa Croce-Carle CuneoUnknownAdvanced Haematological Malignancies | High Risk Haematological MalignanciesItaly
-
AstraZenecaParexelActive, not recruitingAdvanced Haematological MalignanciesSpain, United States, Canada, Korea, Republic of, Poland, Australia, France, United Kingdom, Ireland
-
Istituto Scientifico Romagnolo per lo Studio e...Azienda Unità Sanitaria Locale della RomagnaRecruitingHaematological Malignancy | Haematologic DiseaseItaly
-
Melbourne HealthActive, not recruitingHaematological MalignancyAustralia
-
Assistance Publique - Hôpitaux de ParisMinistry of Health, FranceUnknownHaematological MalignancyFrance
-
Centre Henri BecquerelUnknownHaematological MalignancyFrance
-
Thomas ZilliUniversity Hospital, GenevaRecruitingHaematological MalignancySwitzerland
-
Morten LadekarlRecruitingSolid Tumor, Unspecified, Adult | Haematological MalignancyDenmark
-
RenJi HospitalRecruitingHaematological MalignancyChina
-
Helsinki University Central HospitalRecruitingSolid Tumor | Advanced Cancer | Haematological MalignancyFinland
Clinical Trials on AS703569
-
IBSA Farmaceutici Italia SrlUniversita degli Studi di Catania; Informapro SrlRecruiting
-
Merck KGaA, Darmstadt, GermanyCompleted