Decitabine Maintenance in Elderly Acute Myeloid Leukemia Patients

• Status: Completed
• Trial end date: 2014-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The study aims at determining the feasibility of using maintenance Decitabine therapy following remission induction and consolidation in elderly Acute Myeloid Leukemia patients who are fit for aggressive therapy.

Primary: Safety and tolerability of the decitabine regimen in the post remission state.

Secondary:

1. Disease-free survival - To determine the one-year disease-free survival in elderly patients with acute myeloid leukemia (AML) in complete remission treated with Decitabine as post-consolidation maintenance therapy.

2. Overall survival

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Collaborator: Eisai Inc.
• Treatments: Azacitidine; Decitabine

Criteria

Inclusion Criteria:

1. Patients with AML (excluding Acute Promyelocytic Leukemia) according to the WHO classification, including de novo and secondary AML. Patient must be in complete remission after 1 cycle of induction therapy consisting of cytarabine (100 mg/m2 as a 24 hour infusion for 7 consecutive days) and idarubicin (12 mg/m2 as a slow intravenous push daily for 3 days), and 2 cycles of consolidation therapy (each consisting of cytarabine at a dose of 1 g/m2 given intravenously over 3 hours every 12 hours on days 1,3,and 5).

2. Patients who maintain morphologic complete remission as documented by a bone marrow aspirate/biopsy after consolidation therapy will be eligible to receive Decitabine maintenance therapy. Maintenance therapy should be started as soon as feasible after recovery from the last consolidation cycle but no sooner than 29 days after start of the last consolidation cycle and no later than 60 days after recovery from the last cycle of consolidation therapy.

3. Age ≥ 60 years

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

5. Informed consent, personally signed and dated to participate in the study

6. Be able to comply with study procedures and follow-up examinations

7. Be non-fertile or agree to use birth control during the study through the end of last treatment visit

8. Adequate renal and hepatic function as indicated by all of the following: Total bilirubin ≤ 1.5 institutional Upper Limit of Normal (ULN); and Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN; and Serum creatinine ≤ 1.5 mg/dL

9. Adequate cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) ≥ 50% on multigated acquisition (MUGA) scan, similar radionuclide angiographic scan, or echocardiogram

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL, WHO classification of APL with t(15;17)(q22;q12)

2. Prior diagnosis and treatment for AML, including hematopoietic stem cell transplant (HSCT)

3. Previous therapy with a hypomethylating agent including decitabine or azacitidine (i.e. for an antecedent myelodysplastic syndrome)

4. Any prior therapy for AML except for hydroxyurea for the control of blood counts

5. Psychiatric disorders that would interfere with consent, study participation, or follow-up

6. Cardiac Disease: Heart failure NYHA class 3 or 4; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)

7. Chronically impaired renal function (creatinine clearance < 30 ml / min)

8. Inadequate liver function (ALT and AST ≥ 2.5 x ULN) if not caused by leukemic infiltration

9. Total bilirubin ≥ 1.5 x ULN if not caused by leukemic infiltration

10. Known HIV and/or hepatitis C infection

11. Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy

12. Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders

13. Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)

14. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo therapy on this protocol

15. Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)

16. Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed

17. History of organ allograft

18. Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol

19. Patients who have an indication for and can undergo a non-myeloablative transplant procedure