acute myeloid leukemia
Conditions
Interventions
each daily for 5 days (Days 1-5)
Generic name etc : Low dose Cylocide
INN of investigational material : cytarabine
Therapeutic category code : 422 Antimetabolic agents
Dosage and Administration for In
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Astex Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -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% or more). -Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2. -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. -Subjects must have either PB or BM blasts 5% or more at time of randomization. -Creatinine clearance or glomerular filtration rate 30 mL/min or more 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 while receiving any study therapy and for at least 3 months after completing treatment.
Exclusion criteria
Exclusion criteria: -Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis. -Subjects in first relapse after initial induction who had a response duration more than 12 months OR favorable cytogenetics since those subjects may benefit from re-induction with the same or similar prior regimen. -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 decitabine, azacitidine, or guadecitabine. -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 more than 2.5 * upper limit of normal (ULN; except for subjects with Gilbert's Syndrome for whom direct bilirubin is less than 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 subject 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 more than 2 liters per minute (LPM) oxygen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy OS, defined as the number of days from date of randomization to date of death The primary endpoint of OS will be displayed using a Kaplan-Meier estimate and will be compared between the 2 treatment groups using a log-rank test stratified by the randomization stratification factors with an overall 2-sided alpha level of 0.05. | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy - EFS defined as the number of days from randomization to the earliest of disease progression, treatment discontinuation, start of alternative anti-leukemia therapy (except HCT), or death. - Survival rate at 1 year after randomization. (Subjects will also be followed long term to estimate 2-year survival rate.) - NDAOH. - Transfusion independence rate, calculated based on the number of subjects without red blood cell (RBC) or platelet transfusion for any period of 8 weeks after treatment. - CR rate based on modified International Working Group (IWG) 2003 AML Response Criteria. - CRc (CR+CRi+CRp) rate. - HCT rate. (In subjects who undergo HCT, time to stem cell engraftment and 100-day mortality rate post HCT will also be assessed.) - Duration of CR, defined as the time from first CR to time of relapse. - Health-related QOL by EQ-5D (consisting of the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale [EQ VAS]). - Incidence and severity of adverse events (AEs). - 30- and 60-day all-cause early mortality. | — |
Countries
Asia except Japan, Europe, Japan, North America
Outcome results
None listed