Leukemia, Myeloid, AcutePhase 2NCT01565668
Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 2 study testing AC220 in people with Leukemia, Myeloid, Acute, run by Daiichi Sankyo at 24 sites in 4 countries.
Trial summary
This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- AC220
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 24 sitesin 4 countries
- Study dates
- Apr 2012to Mar 2015
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has morphologically documented primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after hematopoietic stem cell transplantation (HSCT)
- Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio)
- Eastern Cooperative Oncology Group performance status of 0 to 2
- In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT
- Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1
- Patients - both males and females - with reproductive potential are eligible
Who cannot join
- Subject received previous treatment with AC220
- Subject has a diagnosis of acute promyelocytic leukemia
- Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis
- Subject has AML or antecedent MDS secondary to prior chemotherapy
- Subject has had HSCT and has either of the following:
- Donor lymphocyte infusion (DLI) is not permitted during the study or < 30 days prior to study entry
Show all 18Show fewer
- Subject has clinically active central nervous system (CNS) leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated
- Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
- Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450- isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject
- Subject requires treatment with anticoagulant therapy
- Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen
- Subject had major surgery within 4 weeks prior to first dose of AC220
- Subject has uncontrolled or significant cardiovascular disease, including
- Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML)
- Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
- Subject has any of the following laboratory values:
- Subject is a female with a positive pregnancy test, pregnant, or breastfeeding
- Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
Trial locations and contacts
24 sites in 4 countries.
24 sites in 4 countries
United States18 sites
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
John Hopkins University
Baltimore, Maryland, 21231
Tufts University School of Medicine-Tufts Medical Center
Boston, Massachusetts, 02111
Medical University of South Carolina, Hollings Cancer Center
Charleston, South Carolina, 29403
Northwestern University
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
UT Southwestern Medical Center, Simmons Cancer Center
Dallas, Texas, 75390
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
MD Anderson
Houston, Texas, 77030
UCLA School of Medicine
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University, Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Weill Cornell Medical College
New York, New York, 10065
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
France4 sites
CHU d'Angers
Angers, 49033
CHU de Grenoble
Grenoble, 38043
Hôpital Saint Antoine
Paris, 75571
Hôpital Haut Lévêque
Pessac, 33600
Italy1 site
Universitaria Policlinico S. Orsola Malpighi, Institute of Hemtology "L. & A. Seragnoli"
Bologna, 40138
United Kingdom1 site
Nottingham University Hospitals
Nottingham, England
About this study
Official title: A Phase 2, Randomized, Open-Label Study of the Safety and Efficacy of Two Doses of Quizartinib (AC220; ASP2689) in Subjects With FLT3-ITD Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- AC220
- Keywords
- FLT3-ITD positive Acute Myeloid Leukemia (AML), AC220, Relapse, Refractory
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AC220Drug
Also called Quizartinib, ASP2689
oral
| Study group | Role | What they receive |
|---|---|---|
| AC220 Dose Level 1 | Experimental | Not described Receives: Drug: AC220 |
| AC220 Dose Level 2 | Experimental | Not described Receives: Drug: AC220 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population)
CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi).
- Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10^9/L and platelet count ≥100 × 10^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available).
- Participants with CRp must have achieved CR except for incomplete platelet recovery (< 100 ×10^9/L).
- Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia <1 × 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required.
Measured: At end of Cycle 2 (after two complete 28-day cycles post treatment)
Secondary outcomes (8)
Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population)
Participant must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state (< 5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have an absolute neutrophil count (ANC) ≥ 1x10^9/L and platelet count ≥ 100 x 10^9/L and they will be red blood cell (RBC) and platelet transfusion independent (defined as 4 weeks without RBC transfusions and 1 week without platelet transfusion).
Measured: At end of treatment visit (approximately 3 years post treatment)
Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population)
OS was defined as the time from the date of randomization until the date of death from any cause.
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population)
EFS was defined as the time from the date of randomization until the date of documented relapse or death.
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population)
LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc.
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Duration of Remission After Approximately 3 Years (Intent-to-Treat Population)
Duration of remission was defined as the time from first documented remission until documented relapse. CRc was defined as composite complete remission and CRi was defined as complete remission with incomplete hematological recovery.
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population)
Time to CRc was defined as the time from the date of randomization until the first disease assessment of CRc. Time to CRc was only evaluated in participants who achieved CRc.
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population)
Transplantation rate was defined as the percentage of participants who underwent HSCT directly after treatment with quizartinib (no other intervening acute myeloid leukemia therapies other than conditioning regimens for the HSCT).
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set)
QT interval corrected for heart rate using Fridericia's formula (QTcF) grading was to be done according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the definition of Grade 2 or higher prolongation is QTcF more than 480 msec.
Measured: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionMar 2015
- Study completionMar 2015
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.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ambit Biosciences Corporation
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01565668
- Sponsor's protocol ID
- 2689-CL-2004
- Other IDs
- 2011-005408-13
- Status last verified
- Dec 2019
- First submitted
- 27 Mar 2012
- Last updated
- 27 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Open-Label Study of the Safety and Efficacy of Two Doses of Quizartinib (AC220; ASP2689) in Subjects With FLT3-ITD Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT01565668
- Acronym / sponsor ID
- 2689-CL-2004
- Conditions
- Leukemia, Myeloid, Acute
- Keywords
- FLT3-ITD positive Acute Myeloid Leukemia (AML), AC220, Relapse, Refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Collaborators
- Ambit Biosciences Corporation
- Study start
- Apr 2012
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 29 Mar 2012 (estimated)
- Results
- Posted 27 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AC220 Dose Level 1 | Experimental | Drug: AC220 |
| AC220 Dose Level 2 | Experimental | Drug: AC220 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subject has morphologically documented primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after hematopoietic stem cell transplantation (HSCT)
- Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio)
- Eastern Cooperative Oncology Group performance status of 0 to 2
- In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT
- Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1
Key exclusion criteria (18 listed)
- Subject received previous treatment with AC220
- Subject has a diagnosis of acute promyelocytic leukemia
- Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis
- Subject has AML or antecedent MDS secondary to prior chemotherapy
- Subject has had HSCT and has either of the following:
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 |
|---|---|---|
| AC220Also: Quizartinib, ASP2689oral | Drug | AC220 Dose Level 1, AC220 Dose Level 2 |
Primary outcome
Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population)
Time frame: At end of Cycle 2 (after two complete 28-day cycles post treatment)
CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi). * Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10^9/L and platelet count ≥100 × 10^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available). * Participants with CRp must have achieved CR except for incomplete platelet recovery (< 100 ×10^9/L). * Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia <1 × 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required.
8 secondary outcomes
Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population)
Time frame: At end of treatment visit (approximately 3 years post treatment)
Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Duration of Remission After Approximately 3 Years (Intent-to-Treat Population)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set)
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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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.
Global Clinical Leader study director
Daiichi Sankyo
24 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AC220 in people with Leukemia, Myeloid, Acute, run by Daiichi Sankyo at 24 sites in 4 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 6 inclusion and 18 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 27 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, France, Italy, United Kingdom. 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 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?
Yes. Results are posted in the registry (first posted 27 Dec 2019). 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?
Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population) (time frame: At end of Cycle 2 (after two complete 28-day cycles post treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Dec 2019.