Acute Myeloid LeukemiaPhase 3NCT02920008
Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia
A Phase 3 study testing guadecitabine and Treatment Choice (TC) in people with Acute Myeloid Leukemia, run by Astex Pharmaceuticals, Inc. at 95 sites in 15 countries.
Trial summary
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Participants will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- guadecitabine and Treatment Choice (TC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 95 sitesin 15 countries
- Study dates
- 16 Mar 2017to 1 Jun 2020
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult participants ≥18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
- History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow [BM] or peripheral blood [PB] blast counts ≥20%).
- Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.
- Participants with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
- Participants must have either PB or BM blasts ≥5% at time of randomization.
- Creatinine clearance or glomerular filtration rate ≥30 mL/min as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas, such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
- Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment of guadecitabine, decitabine, or azacitidine and for at least 3 months after completing treatment and (b) while receiving treatment with high-intensity TC or LDAC and for at least 6 months after completing treatment.
Who cannot join
- Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.
- Participants who are in first relapse after initial induction, if they had a response duration of >12 months from date when first response first documented or if they are good candidates for HCT.
- BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
- Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.
- Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine.
Show all 13Show fewer
- Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
- Treated with any investigational therapy within 2 weeks of the first dose of study treatment.
- Total serum bilirubin >2.5 × upper limit of normal (ULN; except for participants with Gilbert's Syndrome for whom direct bilirubin is <2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C.
- Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
- Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol.
- Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the participant at an imminent risk of death.
- Participants with high PB blasts >50% AND poor ECOG PS of 2.
Trial locations and contacts
95 sites in 15 countries.
95 sites in 15 countries
Japan17 sites
Akita University Hospital
Akita, 010-8543
Chugoku Central Hospital
Fukuyama-Shi, 720-0001
Tokai University Hospital
Isehara-shi, 259-1193
Saitama Medical Center
Kawagoe-Shi, 350-8550
Kobe City Medical Center General Hospital
Kobe, 650-0047
Japanese Red Cross Kyoto Daini Hospital
Kyoto, 602-8026
University Hospital, Kyoto Prefectural University of Medicine
Kyoto, 602-8566
Gunmaken Saiseikai Maebashi Hospital
Maebashi, 371-0821
Nagasaki University Hospital
Nagasaki, 852-8501
The Japanese Red Cross Nagasaki Genbaku Hospital
Nagasaki, 852-8511
Kindai University Hospital
Osakasayama-Shi, 589-8511
Saga University Hospital
Saga, 849-8501
NTT Medical Center Tokyo
Shinagawa-Ku, 141-8625
Shizuoka Cancer Center
Shizuoka, 411-8777
National Hospital Organization Disaster Medical Center
Tachikawa-Shi, 190-0014
Yamagata University Hospital
Yamagata, 990-9585
University of Fukui Hospital
Yoshida-Gun, 910-1193
United States15 sites
University of New Mexico School of Medicine
Albuquerque, New Mexico, 87106
Roswell Park Cancer Institute
Buffalo, New York, 14263
The University of Chicago Medical Center
Chicago, Illinois, 60637
Baylor Research Institute
Dallas, Texas, 75246
Duke Cancer Institute
Durham, North Carolina, 27710
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601-1915
MD Anderson Cancer Center
Houston, Texas, 77030
Franciscan Research Center
Indianapolis, Indiana, 46237
University of Southern California
Los Angeles, California, 90033
West Virginia University Hospitals, Inc.
Morgantown, West Virginia, 26506
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Weill Cornell Medical College
New York, New York, 10021
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, 73104-5418
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Temple University Hospital
Philadelphia, Pennsylvania, 19111-2433
Spain11 sites
Hospital Clínic de Barcelona
Barcelona, 8036
Hospital de la Santa Creu i Sant Pau
Barcelona, 8041
Hospital Duran i Reynals
Barcelona, 8907
Vall d'Hebron Institut d'Oncologia
Barcelona
Hospital San Pedro de Alcántara
Cáceres, 10003
Hospital Universitario Reina Sofía
Córdoba, 14004
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario Central de Asturias
Oviedo, 33011
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Universitario Dr. Peset
Valencia, 46017
Hospital Universitari i Politècnic La Fe
Valencia, 46026
France9 sites
Centre Hospitalier de la Côte Basque
Bayonne, 64100
Hôpital de la Conception
Marseille, 13385
CHRU Montpellier - Saint Eloi
Montpellier, 34295
Groupe Hospitalier de la Région de Mulhouse et Sud Alsace
Mulhouse, 68100
Hôpital Saint-Louis
Paris, 75475
CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
Pessac, 33604
Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69310
Centre Henri Becquerel
Rouen, 76038
Institut Universitaire du Cancer de Toulouse - Oncopole
Toulouse, 31059
Germany8 sites
Städtisches Klinikum Braunschweig gGmbH
Braunschweig, 38114
Marien Hospital Düsseldorf GmbH
Düsseldorf, 40479
Universitätsklinikum Halle (Saale)
Halle, 6120
Universitätsklinikum Schleswig-Holstein
Kiel, 24105
Universitätsklinikum Leipzig
Leipzig, Saxony, 4103
Medizinischen Fakultät Mannheim der Universität Heidelberg
Mannheim
Klinikum der Universität München
München, 81377
Universitätsklinikum Ulm
Ulm, 89081
South Korea7 sites
Pusan National University Hospital
Busan, 49241
Seoul National University Hospital
Seoul, 3080
Severance Hospital
Seoul, 3722
Asan Medical Center
Seoul, 5505
Samsung Medical Center
Seoul, 6351
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 6591
Ulsan University Hospital (UUH)
Ulsan, 44033
Canada5 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
University of Alberta Hospital
Edmonton, Alberta, T6G 2V2
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Hopital Maisonneuve Rosemont
Montreal, H1T 2M4
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1
Hungary5 sites
SE ÁOK I. sz. Belgyógyászati Klinika
Budapest, 1083
Debreceni Egyetem Klinikai Központ
Debrecen, 4032
Somogy Megyei Kaposi Mór Oktató Kórház
Kaposvár, 7400
Pecsi Tudomanyegyetem Klinikai Központ
Pécs
Szegedi Tudományegyetem
Szeged, 6725
Italy5 sites
IRCCS AOU San Martino - IST
Genova, 16132
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, 20122
Ospedale San Raffaele - Milano
Milan, 20132
A.O.R.N. "A. Cardarelli"
Naples, 80131
A.S.U Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia
Udine, 33100
United Kingdom4 sites
Heart of England NHS Foundation Trust - Heartlands Hospital
Birmingham, B9 5SS
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
East Kent Hospitals University NHS Foundation Trust - Kent and Canterbury Hospital
Canterbury, CT1 3NG
St. James's University Hospital
Leeds, LS9 7TF
Belgium3 sites
AZ Sint-Jan Brugge-Oostende AV
Bruges, 8000
Cliniques Universitaires Saint-Luc
Brussels, 1200
Universitair Ziekenhuis Gent
Ghent, 9000
Denmark2 sites
Aarhus University Hospital
Aarhus C, 8000
Rigshospitalet
Copenhagen, 2100
Ukraine2 sites
Khmelnytskyi Regional Hospital
Khmelnytskyi, 29000
Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho
Poltava, 36011
About this study
Official title: A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Participants will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone:
- High intensity (intermediate or high dose cytarabine [HiDAC]; mitoxantrone, etoposide, and cytarabine [MEC]; or fludarabine, cytarabine, granulocyte colony stimulating factor [G-CSF], +/- idarubicin [FLAG/FLAG-Ida]).
- Low intensity (low dose cytarabine [LDAC], decitabine, or azacitidine).
- BSC.
Read the detailed description
This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and safety of guadecitabine in adults with previously treated acute myeloid leukemia (AML) will be conducted in approximately 20 countries. There will be a 14-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last approximately 2 years. Duration of individual participant participation will vary, and participants may continue to receive treatment for as long as they continue to benefit.
Approximately 404 participants from approximately 100 study centers will be randomly assigned to either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 participants per group). TC is as follows:
- High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida).
- Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine.
- Best Supportive Care (BSC).
Guadecitabine will be given subcutaneous (SC) at a dose of 60 microgram per meter square (mg/m^2) in 28-day cycles. In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. Cycle 2 will be either the 5-day regimen (Days 1-5) or 10-day regimen (Days 1-5 and 8-12) based on assessment of disease response and hematologic recovery at the end of Cycle 1. In subsequent cycles, guadecitabine treatment will be for 5 days only (Days 1-5).
- Conditions
- Acute Myeloid Leukemia
- Being tested
- guadecitabine, Treatment Choice (TC)
- Keywords
- AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3
- 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.
guadecitabineDrug
Also called SGI-110
In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. In Cycle 2, the guadecitabine dose will be 60 mg/m^2 for either 10 days (Days 1-5 and 8-12) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by Day ≥28.
Treatment Choice (TC)Drug
- High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida).
- Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine.
- Best Supportive Care (BSC).
| Study group | Role | What they receive |
|---|---|---|
| guadecitabine | Experimental | Guadecitabine will be given SC at a dose of 60 mg/m^2 in 28-day cycles (delayed as necessary to allow blood count recovery). Receives: Drug: guadecitabine |
| Treatment Choice (TC) | Active comparator | 1. High intensity
2. Low intensity
3. Best supportive care (BSC). Receives: Drug: Treatment Choice (TC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.
Measured: From the date of randomization until the date of death, or approximately 34 months
Secondary outcomes (13)
Event-Free Survival
Event-free survival is defined as number of days from randomization to earliest date of treatment discontinuation (for reasons other than initiation of hematopoietic cell transplant [HCT]), start of alternative anti-leukemia therapy (except HCT), or death.
Measured: From the date of randomization until the date of death, or approximately 38 months
Long-Term Survival
Survival rate at 1 year after randomization; participants were also followed to estimate 2-year survival rate.
Measured: Up to approximately 38 months
Number of Days Alive and Out of the Hospital (NDAOH)
Number of days participants alive and out of hospital during first 6 months of the study.
Measured: 6 months
Transfusion Independence Rate
Number of participants without red blood cells (RBC) or platelet transfusion for any 8-week period after treatment divided by total number of participants in efficacy analysis.
Measured: Baseline up to approximately 38 months
Complete Response Rate
The Complete response (CR) rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as the number of participants with a best response of CR divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.
Measured: Baseline to end of treatment, or approximately 38 months
Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate
The combined CR and CR with partial hematologic recovery rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as number of participants with CR and CR with partial hematologic recovery divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.
Measured: Baseline to end of treatment, or approximately 38 months
Composite Complete Response Rate
Composite complete response rate based on modified IWG 2003 AML Response Criteria defined as number of participants with best response of CR, CR with incomplete platelet recovery (CRp), or CR with incomplete blood count recovery (CRi) divided by total number of participants in efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is ANC ≥1000/μL, platelets ≥100,000/μL, independence from RBC and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. CRp is defined as ANC ≥1000/μL, Platelets <100,000/μL, independence from RBC transfusions over the past week, no leukemic blasts and bone marrow should contain less than 5% blast cells. CRi is defined as ANC <1000/μL, no leukemic blasts and bone marrow should contain less than 5% blast cells.
Measured: Baseline to end of treatment, or approximately 38 months
Hematopoietic Cell Transplant (HCT) Rate
Number of participants who received HCT after randomization divided by total number of participants in efficacy analysis.
Measured: Baseline to long term follow-up or approximately 38 months
Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh)
The time from first CR or CRh to time of relapse (the date of the earliest of the following 3 events):
- relapse (defined as the earliest time point whereby BM assessment or PB assessment by the investigator indicate relapse/disease progression due to confirmed reappearance of leukemic blasts in PB or ≥5% leukemic blasts in BM, or clinical progression determined by the investigator),
- start of alternative therapy (except HCT) or
- death.
Measured: Baseline to end of treatment, or approximately 38 months
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores
Index score is calculated based on 5-level version of the EQ-5D descriptive system using the value set for England.
The range of index score is from -0.281 (for the worst health state, score of 5 for all categories) to 1 (for the best health state, score of 1 for all categories).
Measured: Baseline to 6 months
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score
VAS score is obtained using vertical 20-cm visual analogue scale with the top value of 100 labelled as 'the best health you can imagine' and the bottom value of 0 labelled as 'the worst health you can imagine'.
Measured: Baseline to 6 months
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Measured: From first dose until 30 days after the last dose of study drug, or approximately 38 months
All-Cause Mortality
All-cause mortality in the first 30 days and first 60 days after the start of treatment divided by the total number of participants receiving at least one dose of study treatment.
Measured: From the first dose until 60 days after the first dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2016 (estimated)
- Study start16 Mar 2017
- Primary completion20 Jan 2020
- Study completion1 Jun 2020
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Harold N Keer, MD, PhD, Study director, Astex Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02920008
- Sponsor's protocol ID
- SGI-110-06
- Status last verified
- Jul 2024
- First submitted
- 28 Sep 2016
- Last updated
- 28 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Roboz GJ, Sanz G, Griffiths EA, Yee K, Kantarjian H, Recher C, Byrne MT, Patkowska E, Kim HJ, Thomas X, Moors I, Stock W, Illes A, Fenaux P, Miyazaki Y, Yamauchi T, O'Connell CL, Hao Y, Keer HN, Azab M, Dohner H. Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial. Blood Adv. 2024 Apr 23;8(8):2020-2029. doi: 10.1182/bloodadvances.2023012062.
PubMed 38231126
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02920008
- Acronym / sponsor ID
- SGI-110-06
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Mar 2017 (actual)
- Primary completion
- 20 Jan 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 30 Sep 2016 (estimated)
- Results
- Posted 25 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Participants will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone:
- High intensity (intermediate or high dose cytarabine [HiDAC]; mitoxantrone, etoposide, and cytarabine [MEC]; or fludarabine, cytarabine, granulocyte colony stimulating factor [G-CSF], +/- idarubicin [FLAG/FLAG-Ida]).
- Low intensity (low dose cytarabine [LDAC], decitabine, or azacitidine).
- BSC.
Detailed description
This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and safety of guadecitabine in adults with previously treated acute myeloid leukemia (AML) will be conducted in approximately 20 countries. There will be a 14-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last approximately 2 years. Duration of individual participant participation will vary, and participants may continue to receive treatment for as long as they continue to benefit.
Approximately 404 participants from approximately 100 study centers will be randomly assigned to either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 participants per group). TC is as follows:
- High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida).
- Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine.
- Best Supportive Care (BSC).
Guadecitabine will be given subcutaneous (SC) at a dose of 60 microgram per meter square (mg/m^2) in 28-day cycles. In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. Cycle 2 will be either the 5-day regimen (Days 1-5) or 10-day regimen (Days 1-5 and 8-12) based on assessment of disease response and hematologic recovery at the end of Cycle 1. In subsequent cycles, guadecitabine treatment will be for 5 days only (Days 1-5).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| guadecitabine | Experimental | Drug: guadecitabineGuadecitabine will be given SC at a dose of 60 mg/m^2 in 28-day cycles (delayed as necessary to allow blood count recovery). |
| Treatment Choice (TC) | Active comparator | Drug: Treatment Choice (TC)1. High intensity 2. Low intensity 3. Best supportive care (BSC). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult participants ≥18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.
- History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow [BM] or peripheral blood [PB] blast counts ≥20%).
- Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.
- Participants with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
- Participants must have either PB or BM blasts ≥5% at time of randomization.
Key exclusion criteria (13 listed)
- Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.
- Participants who are in first relapse after initial induction, if they had a response duration of >12 months from date when first response first documented or if they are good candidates for HCT.
- BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
- Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
- Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.
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 |
|---|---|---|
| guadecitabineAlso: SGI-110In Cycle 1, guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. In Cycle 2, the guadecitabine dose will be 60 mg/m^2 for either 10 days (Days 1-5 and 8-12) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by Day ≥28. | Drug | guadecitabine |
| Treatment Choice (TC)* High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide, and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida). * Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine. * Best Supportive Care (BSC). | Drug | Treatment Choice (TC) |
Primary outcome
Overall Survival
Time frame: From the date of randomization until the date of death, or approximately 34 months
Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.
13 secondary outcomes
Event-Free Survival
Time frame: From the date of randomization until the date of death, or approximately 38 months
Long-Term Survival
Time frame: Up to approximately 38 months
Number of Days Alive and Out of the Hospital (NDAOH)
Time frame: 6 months
Transfusion Independence Rate
Time frame: Baseline up to approximately 38 months
Complete Response Rate
Time frame: Baseline to end of treatment, or approximately 38 months
Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate
Time frame: Baseline to end of treatment, or approximately 38 months
Composite Complete Response Rate
Time frame: Baseline to end of treatment, or approximately 38 months
Hematopoietic Cell Transplant (HCT) Rate
Time frame: Baseline to long term follow-up or approximately 38 months
Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh)
Time frame: Baseline to end of treatment, or approximately 38 months
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores
Time frame: Baseline to 6 months
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score
Time frame: Baseline to 6 months
Percentage of Participants With Adverse Events (AEs)
Time frame: From first dose until 30 days after the last dose of study drug, or approximately 38 months
All-Cause Mortality
Time frame: From the first dose until 60 days after the first dose of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38231126Roboz GJ, Sanz G, Griffiths EA, Yee K, Kantarjian H, Recher C, Byrne MT, Patkowska E, Kim HJ, Thomas X, Moors I, Stock W, Illes A, Fenaux P, Miyazaki Y, Yamauchi T, O'Connell CL, Hao Y, Keer HN, Azab M, Dohner H. Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial. Blood Adv. 2024 Apr 23;8(8):2020-2029. doi: 10.1182/bloodadvances.2023012062.
- Individual participant dataSharing planned: No
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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.
Harold N Keer, MD, PhD study director
Astex Pharmaceuticals, Inc.
95 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing guadecitabine and Treatment Choice (TC) in people with Acute Myeloid Leukemia, run by Astex Pharmaceuticals, Inc. at 95 sites in 15 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 7 inclusion and 13 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 28 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 95 sites in Japan, United States, Spain, France, Germany and 10 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 phase mean?
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 25 May 2023). 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?
Overall Survival (time frame: From the date of randomization until the date of death, or approximately 34 months). 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 NCT02920008, 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 28 Aug 2024.