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Trial record 1 of 1 for:    NCT02920008
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Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02920008
Recruitment Status : Active, not recruiting
First Posted : September 30, 2016
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE September 28, 2016
First Posted Date  ICMJE September 30, 2016
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE March 16, 2017
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2017)
Overall survival [ Time Frame: 24 months ]
Number of days from day subject was randomized to date of death, regardless of cause.
Original Primary Outcome Measures  ICMJE
 (submitted: September 28, 2016)
Overall survival [ Time Frame: 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2017)
  • Event-free survival [ Time Frame: 24 months ]
    Number of days from randomization to earliest date of disease progression, treatment discontinuation, start of anti-leukemia therapy, or death.
  • Long-term survival [ Time Frame: 24 months ]
    Survival at one year.
  • Number of days alive and out of the hospital (NDAOH). [ Time Frame: 24 months ]
    Number of days subject alive and out of hospital during first 6 months of the study.
  • Transfusion independence rate [ Time Frame: 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.
  • Complete response rate [ Time Frame: 24 months ]
    Number of subjects with best response of CR divided by total number of subjects in efficacy analysis.
  • Composite complete response [ Time Frame: 24 months ]
    Number of subjects with best response of CR, CRp, or CRi divided by total number of subjects in efficacy analysis.
  • Hematopoietic cell transplant (HCT) rate [ Time Frame: 24 months ]
    Number of subjects who received HCT after randomization divided by total number of subjects in efficacy analysis.
  • Duration of complete response (CR) [ Time Frame: 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.
  • Quality of life [ Time Frame: 6 months ]
    The calculation for EQ-5D-5L index value will be performed according to EuroQol group's EQ-5D-5L User Guide.
  • Incidence and severity of adverse events [ Time Frame: 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.
  • 30- and 60-day all-cause mortality [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2016)
  • Event-free survival [ Time Frame: 24 months ]
  • Long-term survival [ Time Frame: 24 months ]
  • Number of days alive and out of the hospital (NDAOH). [ Time Frame: 24 months ]
  • Transfusion independence rate [ Time Frame: 24 months ]
  • Complete response rate [ Time Frame: 24 months ]
  • Composite complete response [ Time Frame: 24 months ]
  • Hematopoietic cell transplant rate [ Time Frame: 24 months ]
  • Duration of complete response (CR) [ Time Frame: 24 months ]
  • Quality of life [ Time Frame: 24 months ]
  • Incidence and severity of adverse events [ Time Frame: 24 months ]
  • 30- and 60-day all-cause mortality [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • 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 Name: SGI-110
  • Drug: Treatment Choice (TC)
    1. High intensity: Intermediate or high dose cytarabine (HiDAC).
    2. Low intensity:

      • LDAC.
      • Decitabine.
      • Azacitidine.
    3. Best supportive care only: given according to standard and institutional practice.
Study Arms  ICMJE
  • 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).
    Intervention: Drug: guadecitabine
  • Active Comparator: Treatment Choice (TC)
    1. High intensity
    2. Low intensity
    3. Best supportive care (BSC).
    Intervention: Drug: Treatment Choice (TC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 18, 2018)
302
Original Estimated Enrollment  ICMJE
 (submitted: September 28, 2016)
404
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Denmark,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Poland,   Spain,   Sweden,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02920008
Other Study ID Numbers  ICMJE SGI-110-06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Astex Pharmaceuticals, Inc.
Study Sponsor  ICMJE Astex Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Harold N Keer, MD, PhD Astex Pharmaceuticals, Inc.
PRS Account Astex Pharmaceuticals, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP