A clinical trial to assess and compare overall survival (OS) between guadecitabine and treatment choice (TC) in adults with previously treated acute myeloid leukemia (AML)
- Conditions
- Acute Myeloid Leukemia (AML)MedDRA version: 20.0Level: HLTClassification code 10024291Term: Leukaemias acute myeloidSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005256-97-DE
- Lead Sponsor
- Astex Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
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 induction therapy using an intensive chemotherapy regimen, defined as a regimen including cytarabine and an anthracycline, and who are refractory to induction (primary refractory) or in relapse after such 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 (according to recommendations of the Clinical Trial Facilitation Group [CTFG]; see below* for details) 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 with guadecitabine, decitabine, or azacitidine and for at least 3 months after completing treatment and (b) while receiving treatment with highintensity TC or LDAC and for at least 6 months after completing treatment. Contraceptive measures which may be considered highly effective comprise combined hormonal contraception (oral, vaginal, or transdermal) or progestogen-only hormonal contraception(oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence, and surgically successful vasectomy. Abstinence is acceptable only if it is consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of birth control.
* According to recommendations of the CTFG (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf), a woman is considered of childbearing potential (ie, fertile) following menarche and until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
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 response duration of >12 months from date when first response was 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. (Note: Prednisone at any dose for other indications is allowed.)
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method