Haematological MalignanciesPhase 1NCT01080664
A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies
A Phase 1 study testing AS703569 in people with Haematological Malignancies, run by EMD Serono at 10 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Haematological Malignancies
- What is being tested?
- AS703569
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 10 sitesin 5 countries
- Study dates
- Dec 2006to Aug 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
Germany3 sites
Universitatsklinik Frankfurt
Frankfurt am Main, D-60590
Technische Universitat Munchen
München, D-81675
Medizinische Universitatsklinik
Ulm, D-89070
Switzerland3 sites
Kantonsspital Basel
Basel, CH-4031
Hospitaux Universitaires
Geneva, 1211
Kantonsspital St Gallen
Sankt Gallen, 9007
Belgium2 sites
Haematologie UZ Gasthuisberg
Leuven, 3000
Mont-Godinne University Hospital (UCL)
Yvoir, B-5530
United States1 site
CTRC at the UT Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
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.
Read the 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
- Being tested
- AS703569
- Keywords
- AS703569, Aurora Kinase Inhibitor, Haematological malignancies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AS703569Drug
Also called Aurora kinase inhibitor
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
AS703569Drug
Also called Aurora kinase inhibitor
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.
| Study group | Role | What they receive |
|---|---|---|
| Regimen 1 | Experimental | Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle Receives: Drug: AS703569 |
| Regimen 2 | Experimental | Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle Receives: Drug: AS703569 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 42 days or 2 cycles
Secondary outcomes (1)
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.
Measured: minimum 21 days or 1 cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2010 (estimated)
- Study startDec 2006
- Primary completionMar 2010
- Study completionAug 2011
Why it stopped: Please see Purpose Statement below
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Haematological MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Narmyn Rejeb, M.D., Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01080664
- Sponsor's protocol ID
- 27335
- Status last verified
- Oct 2013
- First submitted
- 2 Mar 2010
- Last updated
- 22 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23746966
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose-escalation Study of AS703569 Given Orally to Subjects With Haematological Malignancies
- ClinicalTrials.gov ID
- NCT01080664
- Acronym / sponsor ID
- 27335
- Conditions
- Haematological Malignancies
- Keywords
- AS703569, Aurora Kinase Inhibitor, Haematological malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Please see Purpose Statement below
- Enrolment
- 124 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Mar 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 4 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen 1 | Experimental | Drug: AS703569Regimen 1: AS703569 administered on Days 1, 2, 3 and Days 8, 9, 10 of a 21-day cycle |
| Regimen 2 | Experimental | Drug: AS703569Regimen 2: AS703569 administered on Days 1, 2, 3, 4, 5, 6 of a 21-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AS703569Also: Aurora kinase inhibitorDose 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 | Drug | Regimen 1 |
| AS703569Also: Aurora kinase inhibitorDose 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. | Drug | Regimen 2 |
Primary outcome
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.
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
1 secondary outcome
Treatment-emergent adverse events (TEAE)
Time frame: minimum 21 days or 1 cycle
Results and safety
The study was stopped early (reason given: Please see Purpose Statement below). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2013.
- Derived from this study: PubMed 23746966Graux 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Narmyn Rejeb, M.D. study director
Merck Serono S.A., Geneva
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AS703569 in people with Haematological Malignancies, run by EMD Serono at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Switzerland, Belgium, United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Please see Purpose Statement below). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (DLT) (time frame: 21 days or 1 cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01080664, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2013.