Acute Myeloid LeukemiaPhase 1/2NCT00522990
Study to Assess the Safety of Escalating Doses of AT9283, in Patients With Leukemias
A Phase 1/2 study testing AT9283 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Astex Pharmaceuticals, Inc. at 2 sites in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of AT9283 that can be given to patients who have ALL, AML, CML, high-risk myelodysplastic syndromes, or myelofibrosis with myeloid metaplasia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia
- What is being tested?
- AT9283
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2006to Apr 2009
- Phase
- Phase 1/2
- 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
- Provision of signed written informed consent
- Histological or cytological confirmation of one of the following:
- Relapsed or refractory AML or ALL; acute leukaemia in patients who are unsuitable for or refuse standard therapy
- CML in chronic phase, accelerated phase or blast crisis that is resistant or refractory to standard therapy
- High-risk MDS, defined as the presence of:
- i)Refractory anemia with excess blasts (RAEB, 5-19% bone marrow blasts)
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- or
- ii)RAEB in transformation to AML (RAEBT with 20-30% bone marrow blasts)
- Advanced MMM defined by the presence of one or more of the following features:
- i)Hemoglobin < 10 gm/dL (100 g/L)
- ii)Platelet count < 100 x 109/L
- iii)White blood cell count < 4 x 109/L
- iv)Symptomatic splenomegaly or other disease-related symptoms inadequately controlled by conventional therapies
- ECOG performance status 0, 1 or 2
- Male or female, age 18 years or older
- Negative pregnancy test or history of surgical sterility or evidence of post-menopausal status (post-menopausal status is defined as any of the following: natural menopause with menses >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses
Who cannot join
- Inadequate liver function as demonstrated by serum bilirubin ≥1.5 times the upper limits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) ≥2.5 times the ULRR (or ≥5 times the ULRR in the presence of liver metastases)
- Impaired renal function as demonstrated either by an isolated creatinine value of ≥1.5 times the ULRR OR creatinine clearance < 50 mL/min determined by Cockcroft-Gault formula. Note there is no requirement to determine a formal creatinine clearance if the patient's serum creatinine value is ≥1.5 times the ULRR.
- Radiotherapy or chemotherapy within the 14 days prior to the first dose of AT9283 being administered (Day 1, dose level 1). Planned use of hydroxyurea other than as is permitted as described in section 11.9.
- Receiving an investigational anti-cancer treatment concurrently or within 14 days prior to the start of AT9283 infusion (Day 1)
- Unresolved CTCAE grade 2 or greater toxicity (other than stable toxicity) from previous anti-cancer therapy excluding alopecia
- Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
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- Active, uncontrolled central nervous system disease
- Ischemic heart disease or myocardial infarction or unstable cardiac disease within 3 months of study entry
- Prior infection with human immunodeficiency virus (HIV), hepatitis B or C viruses - screening for viral infections is not required for entry to this study
- Major surgery within 28 days prior to the start of AT9283 infusion (Day 1) - excluding skin biopsies and procedures for insertion of central venous access devices
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase I/IIa Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of AT9283, a Small Molecule Inhibitor of Aurora Kinases, in Patients With Refractory Hematological Malignancies
The goal of this clinical research study is to find the highest tolerable dose of AT9283 that can be given to patients who have ALL, AML, CML, high-risk myelodysplastic syndromes, or myelofibrosis with myeloid metaplasia. Researchers want to perform pharmacokinetic (PK) testing on blood to find out how quickly the study drug leaves the body and how the body breaks down the drug. The safety and effectiveness of this drug will also be studied.
Read the detailed description
Dose escalation study of AT9283 administered to patients with refractory hematological malignancies. Study objectives include identification of MTD and dose limiting toxicities, preliminary assessment of efficacy and definition of pharmacokinetic profile
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndromes, Myelofibrosis
- Being tested
- AT9283
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT9283Drug
Three weekly intravenous administration of AT9283
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Refractory Hematological Malignancies Receives: Drug: AT9283 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Measured: Up to 30 days after completing therapy with AT9283
Secondary outcomes (1)
Pharmacokinetic profile, Safety and tolerability of maximum tolerated dose, efficacy, pharmacodynamic effect, identify dose limiting toxicities
Measured: Within six months of initiating therapy with AT92823
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2007 (estimated)
- Study startSep 2006
- Primary completionApr 2009
- Study completionApr 2009
Why it stopped: Recommended Phase II dose determined
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 Acute Myeloid LeukemiaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00522990
- Sponsor's protocol ID
- AT9283/0002
- Other IDs
- 2006-0177
- Status last verified
- Aug 2024
- First submitted
- 29 Aug 2007
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Foran J, Ravandi F, Wierda W, Garcia-Manero G, Verstovsek S, Kadia T, Burger J, Yule M, Langford G, Lyons J, Ayrton J, Lock V, Borthakur G, Cortes J, Kantarjian H. A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis. Clin Lymphoma Myeloma Leuk. 2014 Jun;14(3):223-30. doi: 10.1016/j.clml.2013.11.001. Epub 2013 Nov 14.
PubMed 24355079
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of AT9283, a Small Molecule Inhibitor of Aurora Kinases, in Patients With Refractory Hematological Malignancies
- ClinicalTrials.gov ID
- NCT00522990
- Acronym / sponsor ID
- AT9283/0002
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndromes, Myelofibrosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recommended Phase II dose determined
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 30 Aug 2007 (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.
The goal of this clinical research study is to find the highest tolerable dose of AT9283 that can be given to patients who have ALL, AML, CML, high-risk myelodysplastic syndromes, or myelofibrosis with myeloid metaplasia. Researchers want to perform pharmacokinetic (PK) testing on blood to find out how quickly the study drug leaves the body and how the body breaks down the drug. The safety and effectiveness of this drug will also be studied.
Detailed description
Dose escalation study of AT9283 administered to patients with refractory hematological malignancies. Study objectives include identification of MTD and dose limiting toxicities, preliminary assessment of efficacy and definition of pharmacokinetic profile
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AT9283Refractory Hematological Malignancies |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Provision of signed written informed consent
- Histological or cytological confirmation of one of the following:
- Relapsed or refractory AML or ALL; acute leukaemia in patients who are unsuitable for or refuse standard therapy
- CML in chronic phase, accelerated phase or blast crisis that is resistant or refractory to standard therapy
- i)Refractory anemia with excess blasts (RAEB, 5-19% bone marrow blasts)
Key exclusion criteria (10 listed)
- Inadequate liver function as demonstrated by serum bilirubin ≥1.5 times the upper limits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) ≥2.5 times the ULRR (or ≥5 times the ULRR in the presence of liver metastases)
- Impaired renal function as demonstrated either by an isolated creatinine value of ≥1.5 times the ULRR OR creatinine clearance < 50 mL/min determined by Cockcroft-Gault formula. Note there is no requirement to determine a formal creatinine clearance if the patient's serum creatinine value is ≥1.5 times the ULRR.
- Radiotherapy or chemotherapy within the 14 days prior to the first dose of AT9283 being administered (Day 1, dose level 1). Planned use of hydroxyurea other than as is permitted as described in section 11.9.
- Receiving an investigational anti-cancer treatment concurrently or within 14 days prior to the start of AT9283 infusion (Day 1)
- Unresolved CTCAE grade 2 or greater toxicity (other than stable toxicity) from previous anti-cancer therapy excluding alopecia
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 |
|---|---|---|
| AT9283Three weekly intravenous administration of AT9283 | Drug | 1 |
Primary outcome
Safety and tolerability
Time frame: Up to 30 days after completing therapy with AT9283
1 secondary outcome
Pharmacokinetic profile, Safety and tolerability of maximum tolerated dose, efficacy, pharmacodynamic effect, identify dose limiting toxicities
Time frame: Within six months of initiating therapy with AT92823
Results and safety
The study was stopped early (reason given: Recommended Phase II dose determined). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2024.
- Results publication: PubMed 24355079Foran J, Ravandi F, Wierda W, Garcia-Manero G, Verstovsek S, Kadia T, Burger J, Yule M, Langford G, Lyons J, Ayrton J, Lock V, Borthakur G, Cortes J, Kantarjian H. A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis. Clin Lymphoma Myeloma Leuk. 2014 Jun;14(3):223-30. doi: 10.1016/j.clml.2013.11.001. Epub 2013 Nov 14.
- Publication of the Study ResultsLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AT9283 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Astex Pharmaceuticals, Inc. at 2 sites in United States.
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 16 inclusion and 10 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 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: Recommended Phase II dose determined). 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?
Safety and tolerability (time frame: Up to 30 days after completing therapy with AT9283). 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 NCT00522990, 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 2 Aug 2024.