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Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

Sponsor
Astex Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02920008
Collaborator
(none)
302
Enrollment
95
Locations
2
Arms
38.5
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Subjects 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and safety of guadecitabine in adults with previously treated 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 subject participation will vary, and subjects may continue to receive treatment for as long as they continue to benefit.

Approximately 404 subjects from approximately 100 study centers will be randomly assigned to either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 subjects 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 SC at a dose of 60 mg/m2 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

Study Type:
Interventional
Actual Enrollment :
302 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 16, 2017
Actual Primary Completion Date :
Jan 20, 2020
Actual Study Completion Date :
Jun 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: guadecitabine

Guadecitabine will be given SC at a dose of 60 mg/m2 in 28-day cycles (delayed as necessary to allow blood count recovery).

Drug: guadecitabine
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/m2 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.
Other Names:
  • SGI-110

    		•
    Active Comparator: Treatment Choice (TC)

    High intensity Low intensity Best supportive care (BSC).

    Drug: Treatment Choice (TC)
    High intensity: Intermediate or high dose cytarabine (HiDAC). Low intensity: LDAC. Decitabine. Azacitidine. Best supportive care only: given according to standard and institutional practice.

    Outcome Measures

    Primary Outcome Measures

    1. Overall survival [24 months]

      Number of days from day subject was randomized to date of death, regardless of cause.

    Secondary Outcome Measures

    1. Event-free survival [24 months]

      Number of days from randomization to earliest date of disease progression, treatment discontinuation, start of anti-leukemia therapy, or death.

    2. Long-term survival [24 months]

      Survival at one year.

    3. Number of days alive and out of the hospital (NDAOH). [24 months]

      Number of days subject alive and out of hospital during first 6 months of the study.

    4. Transfusion independence rate [24 months]

      Number of subjects without RBC or platelet transfusion for any 8-week period after treatment divided by total number of subjects in efficacy analysis.

    5. Complete response rate [24 months]

      Number of subjects with best response of CR divided by total number of subjects in efficacy analysis.

    6. Composite complete response [24 months]

      Number of subjects with best response of CR, CRp, or CRi divided by total number of subjects in efficacy analysis.

    7. Hematopoietic cell transplant (HCT) rate [24 months]

      Number of subjects who received HCT after randomization divided by total number of subjects in efficacy analysis.

    8. Duration of complete response (CR) [24 months]

      Duration of CR (in number of days) will be calculated from the first time a CR is observed to time of relapse (defined as the earliest time point whereby BM assessment or PB assessment indicate relapse/disease progression due to confirmed reappearance of ≥5% leukemic blasts in PB or ≥5% leukemic blasts in BM.

    9. Quality of life [6 months]

      The calculation for EQ-5D-5L index value will be performed according to EuroQol group's EQ-5D-5L User Guide.

    10. Incidence and severity of adverse events [24 months]

      Subject reported and investigator-observed AEs and 30- and 60-day all-cause mortality, along with clinical laboratory tests (hematology, chemistries), concomitant Medications, physical examination, vital signs, ECOG performance status and ECGs.

    11. 30- and 60-day all-cause mortality [24 months]

      Number of deaths, regardless of cause, within 30 or 60 days from the first study dose divided by the total number of subjects included in the safety analysis set.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Adult subjects ≥18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure.

    2. 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%).

    3. Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.

    4. Subjects 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.

    5. Subjects must have either PB or BM blasts ≥5% at time of randomization.

    6. 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).

    7. 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.

    Exclusion Criteria:

    1. Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis.

    2. Subjects 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.

    3. BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).

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

    5. Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.

    6. Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine.

    7. Hypersensitivity to decitabine, guadecitabine, or any of their excipients.

    8. Treated with any investigational therapy within 2 weeks of the first dose of study treatment.

    9. Total serum bilirubin >2.5 × upper limit of normal (ULN; except for subjects 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.

    10. 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.

    11. 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.

    12. 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 subject at an imminent risk of death.

    13. Subjects with high PB blasts >50% AND poor ECOG PS of 2.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Southern California Los Angeles California United States 90033
    2 The University of Chicago Medical Center Chicago Illinois United States 60637
    3 Franciscan Research Center Indianapolis Indiana United States 46237
    4 John Theurer Cancer Center at Hackensack University Medical Center Hackensack New Jersey United States 07601-1915
    5 University of New Mexico School of Medicine Albuquerque New Mexico United States 87106
    6 Roswell Park Cancer Institute Buffalo New York United States 14263
    7 Weill Cornell Medical College New York New York United States 10021
    8 Duke Cancer Institute Durham North Carolina United States 27710
    9 University of Oklahoma Medical Center Oklahoma City Oklahoma United States 73104-5418
    10 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
    11 Temple University Hospital Philadelphia Pennsylvania United States 19111-2433
    12 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    13 Baylor Research Institute Dallas Texas United States 75246
    14 MD Anderson Cancer Center Houston Texas United States 77030
    15 West Virginia University Hospitals, Inc. Morgantown West Virginia United States 26506
    16 AZ Sint-Jan Brugge-Oostende AV Brugge Belgium 8000
    17 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
    18 Universitair Ziekenhuis Gent Gent Belgium 9000
    19 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    20 University of Alberta Hospital Edmonton Alberta Canada T6G 2V2
    21 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2C1
    22 McGill University Health Centre Montreal Quebec Canada H4A 3J1
    23 Hopital Maisonneuve Rosemont Montreal Canada H1T 2M4
    24 Aarhus University Hospital Aarhus C Denmark 8000
    25 Rigshospitalet Copenhagen Denmark 2100
    26 Centre Hospitalier de la Côte Basque Bayonne France 64100
    27 Hôpital de la Conception Marseille France 13385
    28 CHRU Montpellier - Saint Eloi Montpellier France 34295
    29 Groupe Hospitalier de la Région de Mulhouse et Sud Alsace Mulhouse France 68100
    30 Hôpital Saint-Louis Paris France 75475
    31 CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque Pessac France 33604
    32 Centre Hospitalier Lyon-Sud Pierre Bénite France 69310
    33 Centre Henri Becquerel Rouen cedex 1 France 76038
    34 Institut Universitaire du Cancer de Toulouse - Oncopole Toulouse France 31059
    35 Universitätsklinikum Leipzig Leipzig Sachsen Germany 4103
    36 Städtisches Klinikum Braunschweig gGmbH Braunschweig Germany 38114
    37 Marien Hospital Düsseldorf GmbH Düsseldorf Germany 40479
    38 Universitätsklinikum Halle (Saale) Halle Germany 6120
    39 Universitätsklinikum Schleswig-Holstein Kiel Germany 24105
    40 Medizinischen Fakultät Mannheim der Universität Heidelberg Mannheim Germany
    41 Klinikum der Universität München Muenchen Germany 81377
    42 Universitätsklinikum Ulm Ulm Germany 89081
    43 SE ÁOK I. sz. Belgyógyászati Klinika Budapest Hungary 1083
    44 Debreceni Egyetem Klinikai Központ Debrecen Hungary 4032
    45 Somogy Megyei Kaposi Mór Oktató Kórház Kaposvar Hungary 7400
    46 Pecsi Tudomanyegyetem Klinikai Központ Pécs Hungary
    47 Szegedi Tudományegyetem Szeged Hungary 6725
    48 IRCCS AOU San Martino - IST Genova Italy 16132
    49 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano Italy 20122
    50 Ospedale San Raffaele - Milano Milano Italy 20132
    51 A.O.R.N. "A. Cardarelli" Napoli Italy 80131
    52 A.S.U Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia Udine Italy 33100
    53 Akita University Hospital Akita-shi Japan 010-8543
    54 Chugoku Central Hospital Fukuyama-Shi Japan 720-0001
    55 Tokai University Hospital Isehara-shi Japan 259-1193
    56 Saitama Medical Center Kawagoe-Shi Japan 350-8550
    57 Kobe City Medical Center General Hospital Kobe-shi Japan 650-0047
    58 Japanese Red Cross Kyoto Daini Hospital Kyoto-shi Japan 602-8026
    59 University Hospital, Kyoto Prefectural University of Medicine Kyoto-shi Japan 602-8566
    60 Gunmaken Saiseikai Maebashi Hospital Maebashi-shi Japan 371-0821
    61 Nagasaki University Hospital Nagasaki-shi Japan 852-8501
    62 The Japanese Red Cross Nagasaki Genbaku Hospital Nagasaki-Shi Japan 852-8511
    63 Kindai University Hospital Osakasayama-Shi Japan 589-8511
    64 Saga University Hospital Saga-shi Japan 849-8501
    65 NTT Medical Center Tokyo Shinagawa-Ku Japan 141-8625
    66 Shizuoka Cancer Center Shizuoka Japan 411-8777
    67 National Hospital Organization Disaster Medical Center Tachikawa-Shi Japan 190-0014
    68 Yamagata University Hospital Yamagata-Shi Japan 990-9585
    69 University of Fukui Hospital Yoshida-Gun Japan 910-1193
    70 Pusan National University Hospital Busan Korea, Republic of 49241
    71 Seoul National University Hospital Seoul Korea, Republic of 3080
    72 Severance Hospital Seoul Korea, Republic of 3722
    73 Asan Medical Center Seoul Korea, Republic of 5505
    74 Samsung Medical Center Seoul Korea, Republic of 6351
    75 The Catholic University of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 6591
    76 Ulsan University Hospital (UUH) Ulsan Korea, Republic of 44033
    77 Instytut Hematologii i Transfuzjologi Warszawa Poland 02-776
    78 Hospital Clínic de Barcelona Barcelona Spain 8036
    79 Hospital de la Santa Creu i Sant Pau Barcelona Spain 8041
    80 Hospital Duran i Reynals Barcelona Spain 8907
    81 Vall d'Hebron Institut d'Oncologia Barcelona Spain
    82 Hospital San Pedro de Alcántara Cáceres Spain 10003
    83 Hospital Universitario Reina Sofía Córdoba Spain 14004
    84 Hospital General Universitario Gregorio Marañón Madrid Spain 28007
    85 Hospital Universitario Central de Asturias Oviedo Spain 33011
    86 Hospital Universitario Virgen del Rocío Sevilla Spain 41013
    87 Hospital Universitario Dr. Peset Valencia Spain 46017
    88 Hospital Universitari i Politècnic La Fe Valencia Spain 46026
    89 Sahlgrenska University Hospital Göteborg Sweden 413 45
    90 Khmelnytskyi Regional Hospital Khmelnytskyi Ukraine 29000
    91 Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho Poltava Ukraine 36011
    92 Heart of England NHS Foundation Trust - Heartlands Hospital Birmingham United Kingdom B9 5SS
    93 University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre Bristol United Kingdom BS2 8ED
    94 East Kent Hospitals University NHS Foundation Trust - Kent and Canterbury Hospital Canterbury United Kingdom CT1 3NG
    95 St. James's University Hospital Leeds United Kingdom LS9 7TF

    Sponsors and Collaborators

    • Astex Pharmaceuticals, Inc.

    Investigators

    • Study Director: Harold N Keer, MD, PhD, Astex Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Astex Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02920008
    Other Study ID Numbers:
    • SGI-110-06
    First Posted:
    Sep 30, 2016
    Last Update Posted:
    Sep 9, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Astex Pharmaceuticals, Inc.
    AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Guadecitabine

    Study Results

    No Results Posted as of Sep 9, 2021