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

• Status: Completed
• Trial end date: 2020-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Astex Pharmaceuticals; Astex Pharmaceuticals, Inc.
• Treatments: Guadecitabine

Criteria

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.