Status:
COMPLETED
Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Adult Acute Megakaryoblastic Leukemia
Adult Acute Monoblastic Leukemia
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
This randomized phase II trial studies how well cytarabine with or without SCH 900776 works in treating adult patients with relapsed acute myeloid leukemia. Drugs used in chemotherapy, such as cytarab...
Detailed Description
PRIMARY OBJECTIVES: I. To compare the rates of complete remission (CR) plus CR with incomplete recovery (CRi) achieved with cytosine arabinoside (ara-C) (cytarabine) plus the checkpoint kinase 1 (CHK...
Eligibility Criteria
Inclusion
- Adults with the established, pathologically confirmed diagnosis of relapsed AML
- AML that has relapsed at least once or is primary induction failure
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patients must be able to give informed consent
- Female patients of childbearing age must have negative pregnancy test
- Serum creatinine =\< 2.0 mg/dl
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 x upper limit normal (ULN), unless due to Gilbert's, hemolysis or leukemic infiltration
- Alkaline phosphatase =\< 5 x ULN, unless due to Gilbert's, hemolysis or leukemic infiltration
- Bilirubin =\< 2.0 mg/dl, unless due to Gilbert's, hemolysis or leukemic infiltration
- Left ventricular ejection fraction \>= 45% by multi gated acquisition scan (MUGA) or echocardiogram
- Baseline Fridericia corrected QT (QTcF) \< 480 msec
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 30 days after study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are \>= 4 weeks from stem cell infusion, have no active graft-vs-host disease (GVHD), and meet other eligibility criteria
- Patients who fail primary induction therapy or relapse after achieving complete remission (CR) are eligible if they have undergone no more than 2 prior cytotoxic regimens (a regimen is described as a distinctive planned collection of agent\[s\] and/or modalities to be utilized together during a cycle or course of therapy; i.e., induction+consolidation with or without stem cell transplant \[SCT\]), \>= 2 weeks off cytotoxic chemotherapy, and \>= 2 weeks off radiation therapy; patients must be off biologic therapies including hematopoietic growth factors \>= 2 weeks; if using hydroxyurea (HU), steroids, imatinib or other tyrosine kinase inhibitors (TKIs), interferon, or other non-cytotoxics for blast count control, patient must be off for \>= 24 hours (hrs) before starting MK-8776
- Fluvoxamine and ciprofloxacin must be stopped 7 days prior to day 1 of therapy, and be excluded during administration of study therapy; if the subject is using any of the other drugs that are cytochrome P4501A2 (CYP1A2) or P-glycoprotein (PgP) inhibitors, substitution should be considered and administration of these drugs should be avoided on the days of administration of MK-8776; in addition, smoking should be avoided and cytochrome P450 3A4 (CYP3A4) substrates with a narrow therapeutic index should be avoided: alfentanil, astemizole, cisapride, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine
Exclusion
- Any previous treatment with MK-8776
- Considered refractory or treatment failure to most recent treatment regimen, unless primary refractory
- Concomitant chemotherapy, radiation therapy, or immunotherapy
- Hyperleukocytosis with \>= 50,000 blasts/uL (if using HU, steroids, tyrosine kinase/src inhibitors (including fms-related tyrosine kinase 3 \[FLT3\] inhibitors), arsenic, interferon or leukapheresis for blast count control, patient must be off those agents for 24 hours prior to beginning ara-C +/- MK-8776)
- Acute progranulocytic leukemia (APL, M3)
- Active disseminated intravascular coagulation (DIC)
- Active central nervous system (CNS) leukemia
- Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
- Presence of other life-threatening illness
- Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-8776
- History of Fridericia corrected QT (QTcF) prolongation greater than grade 1 or 480 msec
- Subjects with the following cardiac risk factors must be excluded: transmural myocardial infarction (MI) within prior 6 months, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack (TIA) or seizure disorder within 6 months prior to study drug administration
- Subjects with history of risk factors for torsades de pointes: clinical history of heart failure (New York Heart Association \[NYHA\] class III or IV), hypo- or hyper-kalemia or hypomagnesemia (supplementation to bring levels within normal limits prior to administration of MK-8776 is acceptable) or family history of Long QT Syndrome
- Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy or who have a prior history of acquired immunodeficiency syndrome (AIDS) indicator conditions, other than history of lymphoma more than 3 years remote
Key Trial Info
Start Date :
May 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 1 2014
Estimated Enrollment :
32 Patients enrolled
Trial Details
Trial ID
NCT01870596
Start Date
May 1 2013
End Date
December 1 2014
Last Update
September 1 2016
Active Locations (5)
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1
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
2
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
3
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
4
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287