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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02348489




Registration number
NCT02348489
Ethics application status
Date submitted
22/01/2015
Date registered
28/01/2015
Date last updated
14/01/2021

Titles & IDs
Public title
SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction
Scientific title
A Phase 3, Multicenter, Open-label, Randomized Study of SGI-110 Versus Treatment Choice (TC) in Adults With Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Considered Candidates for Intensive Remission Induction Chemotherapy
Secondary ID [1] 0 0
SGI-110-04
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myeloid, Acute 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SGI-110 (guadecitabine)
Treatment: Drugs - Treatment Choice

Experimental: SGI-110 (guadecitabine) - Guadecitabine 60 mg/m^2 administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.

Active Comparator: Treatment Choice - One of the following treatment regimens: 20 mg cytarabine administered subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.


Treatment: Drugs: SGI-110 (guadecitabine)
Investigational medicinal product

Treatment: Drugs: Treatment Choice
Choice of one: cytarabine, decitabine, or azacitidine

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With a Complete Response (CR) - Number of participants with a best response of CR assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.
Timepoint [1] 0 0
Up to 38 months (median follow-up of 25.5 months)
Primary outcome [2] 0 0
Overall Survival - Survival time was defined as the number of days from the day the participant was randomly assigned to study treatment to the date of death, regardless of cause.
Timepoint [2] 0 0
At 676 death events (up to 38 months)
Secondary outcome [1] 0 0
Number of Participants With Composite CR (CRc) - CRc is reported as the number of participants with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi).
Timepoint [1] 0 0
Up to 38 months (median follow-up of 25.5 months)
Secondary outcome [2] 0 0
Number of Days Alive and Out of the Hospital - The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital (NDAOH) was calculated as: NDAOH=180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.
Timepoint [2] 0 0
Month 6
Secondary outcome [3] 0 0
Progression-free Survival (PFS) - Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, participant receiving an alternative anti-leukemia therapy (including hematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause.
Timepoint [3] 0 0
Up to 38 months (median follow-up of 25.5 months)
Secondary outcome [4] 0 0
Number of Red Blood Cell or Platelet Transfusions - The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.
Timepoint [4] 0 0
Month 6
Secondary outcome [5] 0 0
Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-5D-5L - EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. Mean change in scores from baseline are summarized in which an index score of 0 represents the worst health state and 1 represents the best health state.
Timepoint [5] 0 0
Baseline to Month 6
Secondary outcome [6] 0 0
Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-VAS - EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarized.
Timepoint [6] 0 0
Baseline to Month 6
Secondary outcome [7] 0 0
Duration of CR - Duration of CR (in number of days) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or = 5% leukemic blasts in BM.
Timepoint [7] 0 0
Up to 38 months (median follow-up of 25.5 months)

Eligibility
Key inclusion criteria
Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic
leukemia) according to World Health Organization (WHO) classification.

Performance status (ECOG) of 0-3. Adults with previously untreated AML except for
hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for
myelodysplastic syndrome (MDS) is allowed.

Not considered candidates for intensive remission induction chemotherapy at time of
enrollment based on EITHER:

1. =75 years of age OR

2. <75 years of age with at least 1 of the following:

i. Poor performance status (ECOG) score of 2-3.

ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:

1. Left ventricular ejection fraction (LVEF) =50%.

2. Lung diffusing capacity for carbon monoxide (DLCO) =65% of expected.

3. Forced expiratory volume in 1 second (FEV1) =65% of expected.

4. Chronic stable angina or congestive heart failure controlled with medication.

iii. Liver transaminases >3 × upper limit of normal (ULN).

iv. Other contraindication(s) to anthracycline therapy (must be documented).

v. Other comorbidity the investigator judges incompatible with intensive remission
induction chemotherapy, which must be documented and approved by the study medical monitor
before randomization.

Creatinine clearance as estimated by the Cockcroft-Gault (C-G) or other medically
acceptable formulas =30 mL/min.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Candidate for intensive remission induction chemotherapy at the time of enrollment.

Candidate for best supportive care only, ie, not a candidate for any active therapy with
the TC comparators.

Known extramedullary central nervous system (CNS) AML.

Second malignancy currently requiring active therapy except breast or prostate cancer
stable on or responding to endocrine therapy.

Prior treatment with decitabine or azacitidine.

Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.

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
subject to high risk of noncompliance with the protocol.

Refractory congestive heart failure unresponsive to medical treatment; active infection
resistant to all antibiotics; or advanced pulmonary disease requiring >2 liters per minute
(LPM) oxygen.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
- Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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United States of America
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Illinois
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Kansas
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Minnesota
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New Jersey
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New Mexico
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United States of America
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New York
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North Carolina
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Ohio
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Pennsylvania
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Tennessee
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Texas
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United States of America
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Wisconsin
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Austria
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Styria
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Austria
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Vienna
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Belgium
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Hainaut
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Belgium
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Oost-vlaanderen
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Belgium
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West-vlaanderen
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Plovdiv
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Bulgaria
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Varna
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Alberta
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British Columbia
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Canada
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Ontario
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Czechia
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Jihormoravsky KRAJ
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Czechia
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Praha
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Czechia
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Praha 10
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Aarhus
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Copenhagen
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Denmark
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Odense
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Finland
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Southern Finland
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Finland
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Helsinki
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France
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Alsace
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France
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Aquitaine
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France
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Haute-normandie
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France
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Ile-de-france
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Limousin, Lorraine
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Midi-pyrenees
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France
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PAYS DE LA Loire
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France
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Provence Alpes COTE D'azur
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France
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Rhone-alpes
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Germany
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Baden-wuerttemberg
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Nordrhein-westfalen
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Germany
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Schleswig-holstein
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Hungary
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Bacs-kiskun
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Hungary
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Budapest
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Debrecen
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Kaposvár
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Italy
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Pesaro E Urbino
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Italy
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Potenza
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Italy
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Torino
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Italy
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Alessandria
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Italy
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Bologna
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Italy
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Busto Arsizio
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Italy
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Catania
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Genova
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Italy
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Milano
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Modena
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Napoli
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Roma
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Udine
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Chubu
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Chugoku
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Kanto
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Kinki
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Kyushu
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Tohoku
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Korea, Republic of
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Gyeonggi-do
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Jeollanam-do
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Mazowieckie
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Opolskie
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Slaskie
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Romania
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Mures
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Romania
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Iasi
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Russian Federation
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Ekaterinburg
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Russian Federation
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Ryazan
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Russian Federation
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Saratov
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Serbia
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Belgrade
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Serbia
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Novi Sad
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Spain
State/province [90] 0 0
Asturias
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Spain
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Barcelona
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Spain
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Caceres
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Spain
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Granada
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Spain
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Madrid
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Spain
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Salamanca
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Spain
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Sevilla
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Spain
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Valencia
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Sweden
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Skane
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Sweden
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Stockholm
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Taiwan
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Taoyuan
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Taiwan
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Taichung
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Taiwan
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Taipei
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United Kingdom
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England
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United Kingdom
State/province [104] 0 0
Kent

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Astex Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To compare efficacy and safety between SGI-110 and Treatment Choice in adults with previously
untreated AML who are not considered candidates for intensive remission induction
chemotherapy.
Trial website
https://clinicaltrials.gov/show/NCT02348489
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
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Email 0 0
Contact person for scientific queries

Summary results
Other publications