Acute Myeloid LeukemiaPhase 2/3SPARK-AML1NCT00952588
Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients
A Phase 2/3 study testing AZD1152 and LDAC in people with Acute Myeloid Leukemia, run by AstraZeneca at 45 sites in 9 countries.
Trial summary
The purpose of this study is to assess the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in AML patients. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- AZD1152 and LDAC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 45 sitesin 9 countries
- Study dates
- Jul 2009to Jun 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent
- Newly diagnosed male or female patients aged 60 and over
- De Novo or Secondary AML
- Not eligible for intensive induction with anthracycline-based combination chemotherapy as a result of at least one of the following:Age ≥75 years; Adverse cytogenetics, e.g., as defined by the MRC Prognostic Groupings; WHO performance status >2; Organ dysfunction arising from significant co-morbidities not directly linked to leukaemia
Who cannot join
- Participation in another clinical study in which an investigational product was received within 14 days before the first dose in this study, or at any time if the patient has not recovered from side-effects associated with that investigational product
- Administration of LDAC is clinically contraindicated
- Patients with AML of FAB M3 classification Acute Promyelocytic Leukaemia (APL)
- Patients with blast crisis of chronic myeloid leukaemia
Trial locations and contacts
45 sites in 9 countries.
45 sites in 9 countries
United States8 sites
Research Site
Atlanta, Georgia
Research Site
Chicago, Illinois
Research Site
Cleveland, Ohio
Research Site
Greenville, South Carolina
Research Site
Houston, Texas
Research Site
Nashville, Tennessee
Research Site
New York, New York
Research Site
Portland, Oregon
Japan7 sites
Research Site
Chūō, Tokyo
Research Site
Fukuoka
Research Site
Isehara, Kanagawa
Research Site
Maebashi, Gunma
Research Site
Nagoya, Aichi-ken
Research Site
Yokohama, Kanagawa
Research Site
Yoshida-gun, Fukui
France6 sites
Research Site
Angers
Research Site
Clermont-Ferrand
Research Site
Grenoble
Research Site
Lyon
Research Site
Marseille
Research Site
Nantes
Spain6 sites
Research Site
Badalona(barcelona), Catalonia
Research Site
Barcelona, Catalonia
Research Site
Madrid, Madrid
Research Site
Majadahonda, Madrid
Research Site
Oviedo, Principality of Asturias
Research Site
Valencia, Valencia
Germany5 sites
Research Site
Duisburg
Research Site
Erlangen
Research Site
Frankfurt
Research Site
Münster
Research Site
Villingen-Schwenningen
Italy5 sites
Research Site
Bologna, BO
Research Site
Genova, GE
Research Site
Orbassano, TO
Research Site
Roma
Research Site
Udine, UD
Australia4 sites
Research Site
Herston, Queensland
Research Site
Melbourne, Victoria
Research Site
Parkville, Victoria
Research Site
Westmead, New South Wales
About this study
Official title: A Randomised, Open-label, Multi-centre, 2-stage, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC) in Comparison With LDAC Alone in Patients Aged ≥ 60 With Newly Diagnosed Acute Myeloid Leukaemia (AML)
The purpose of this study is to assess the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in AML patients.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- AZD1152, LDAC
- Keywords
- Acute Myeloid Leukaemia,, AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD1152Drug
1200 mg, iv, 7 day infusion
LDACDrug
20 mg, sc, bd, 10 days
| Study group | Role | What they receive |
|---|---|---|
| AZD1152 1200 mg | Experimental | AZD1152 1200 mg, iv, 7 day infusion monotherapy Receives: Drug: AZD1152 |
| LDAC 20 mg | Active comparator | LDAC 20 mg, sc, bd, 10 days (400mg per cycle) Receives: Drug: LDAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Overall Complete Response for Stage I
Percentage of patients achieving either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi). Per Cheson Criteria: Confirmed complete remission (CRi) is defined as a disappearance of blasts in the peripheral blood; a decrease in bone marrow blasts to <5% total bone marrow nucleated cells demonstrated in bone marrow aspirate; absence of Auer rods; no persistent extramedullary leukaemia. Complete response (CR) is defined as all requirements to meet CRi and in addition: recovery of neutrophils to ≥1.0 x 109/L and platelets to ≥100 x 109/L; transfusion-independence.
Measured: IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Secondary outcomes (6)
Duration of Response (DoR): Stage I and Transition Phase
DoR was defined for the median of days which showed a confirmed CRi or CR, as the time from first documented evidence of CRi or CR until the first documented sign of disease progression or death. Duration of Response was measured from the Response Start date until evidence of patient relapse or death. Stage I : 45 patients randomized in a 2:1 ratio to AZD1152 or LDAC. Transition phase: enrollment of up to 30 additional patients randomized as per stage I.
Measured: DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Disease Free Survival (DFS)
Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.
Measured: DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Time To Complete Response (TTCR)
TTCR is measured as time from randomization to either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi)
Measured: Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Overall Survival (OS)
Overall Survival is defined as the median time from randomisation to death from any cause. Patients who were not known to have died at the time of the analysis were censored at the date they were last known to be alive.
Measured: Assessed from randomisation until the date of death from any cause, assessed up to 24 months
Percent of Patients With Worsened Trial Outcome Index (TOI)
TOI is derived from the sum of the Functional Well Being (FWB), Physical Well Being (PWB) and additional subscales of the FACT-Leu. The TOI subscale consists of 31 items with TOI scores ranging from 0 to 124. The TOI is described as a summary measure of HRQoL. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -9.
Measured: TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.
The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -11.
Measured: FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Stockman, Study director, AstraZenecaHagop Kantarjian, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00952588
- Sponsor's protocol ID
- D1531C00009
- Acronym
- SPARK-AML1
- Status last verified
- Feb 2020
- First submitted
- 4 Aug 2009
- Last updated
- 24 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Quintas-Cardama A, Ravandi F, Liu-Dumlao T, Brandt M, Faderl S, Pierce S, Borthakur G, Garcia-Manero G, Cortes J, Kantarjian H. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood. 2012 Dec 6;120(24):4840-5. doi: 10.1182/blood-2012-06-436055. Epub 2012 Oct 15.
PubMed 23071272
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open-label, Multi-centre, 2-stage, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC) in Comparison With LDAC Alone in Patients Aged ≥ 60 With Newly Diagnosed Acute Myeloid Leukaemia (AML)
- ClinicalTrials.gov ID
- NCT00952588
- Acronym / sponsor ID
- SPARK-AML1 / D1531C00009
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukaemia,, AML
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 6 Aug 2009 (estimated)
- Results
- Posted 31 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in AML patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD1152 1200 mg | Experimental | Drug: AZD1152AZD1152 1200 mg, iv, 7 day infusion monotherapy |
| LDAC 20 mg | Active comparator | Drug: LDACLDAC 20 mg, sc, bd, 10 days (400mg per cycle) |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Provision of written informed consent
- Newly diagnosed male or female patients aged 60 and over
- De Novo or Secondary AML
- Not eligible for intensive induction with anthracycline-based combination chemotherapy as a result of at least one of the following:Age ≥75 years; Adverse cytogenetics, e.g., as defined by the MRC Prognostic Groupings; WHO performance status >2; Organ dysfunction arising from significant co-morbidities not directly linked to leukaemia
Key exclusion criteria (4 listed)
- Participation in another clinical study in which an investigational product was received within 14 days before the first dose in this study, or at any time if the patient has not recovered from side-effects associated with that investigational product
- Administration of LDAC is clinically contraindicated
- Patients with AML of FAB M3 classification Acute Promyelocytic Leukaemia (APL)
- Patients with blast crisis of chronic myeloid leukaemia
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 |
|---|---|---|
| AZD11521200 mg, iv, 7 day infusion | Drug | AZD1152 1200 mg |
| LDAC20 mg, sc, bd, 10 days | Drug | LDAC 20 mg |
Primary outcome
Percentage of Patients With Overall Complete Response for Stage I
Time frame: IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Percentage of patients achieving either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi). Per Cheson Criteria: Confirmed complete remission (CRi) is defined as a disappearance of blasts in the peripheral blood; a decrease in bone marrow blasts to <5% total bone marrow nucleated cells demonstrated in bone marrow aspirate; absence of Auer rods; no persistent extramedullary leukaemia. Complete response (CR) is defined as all requirements to meet CRi and in addition: recovery of neutrophils to ≥1.0 x 109/L and platelets to ≥100 x 109/L; transfusion-independence.
6 secondary outcomes
Duration of Response (DoR): Stage I and Transition Phase
Time frame: DoR was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Disease Free Survival (DFS)
Time frame: DFS was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Time To Complete Response (TTCR)
Time frame: Response was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Overall Survival (OS)
Time frame: Assessed from randomisation until the date of death from any cause, assessed up to 24 months
Percent of Patients With Worsened Trial Outcome Index (TOI)
Time frame: TOI was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.
Time frame: FACT-Leu was measured every 28 days from randomization for study duration (24 months, between 2009 - 2011)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23071272Quintas-Cardama A, Ravandi F, Liu-Dumlao T, Brandt M, Faderl S, Pierce S, Borthakur G, Garcia-Manero G, Cortes J, Kantarjian H. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood. 2012 Dec 6;120(24):4840-5. doi: 10.1182/blood-2012-06-436055. Epub 2012 Oct 15.
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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.
Paul Stockman study director
AstraZeneca
Hagop Kantarjian principal investigator
M.D. Anderson Cancer Center
45 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AZD1152 and LDAC in people with Acute Myeloid Leukemia, run by AstraZeneca at 45 sites in 9 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 4 inclusion and 4 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: finished, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Japan, France, Spain, Germany and 4 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Patients With Overall Complete Response for Stage I (time frame: IWG Cheson criteria every 28 days from randomization for study duration (24 months, between 2009 - 2011)). 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 NCT00952588, 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 24 Feb 2020.