Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This randomized phase II trial studies how well choline magnesium trisalicylate with idarubicin and cytarabine works in treating patients with acute myeloid leukemia. Drugs used in chemotherapy, such as choline magnesium trisalicylate, idarubicin, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet know whether choline magnesium trisalicylate and combination chemotherapy is more effective than combination chemotherapy alone in treating patients with acute myeloid leukemia.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine temporal changes in leukemic cell nuclear factor of kappa light chain enhancer of B-cells 1 (NF-kB) activity when salicylate (choline magnesium trisalicylate) is administered to patients with acute myeloid leukemia (AML) during induction chemotherapy. II. To determine toxicities associated with administration of salicylate in the setting of induction chemotherapy. III. To determine if salicylate alters the expression of NF-kB-regulated genes in AML cells. IV. To determine if NF-kB modulation by salicylate alters AML chemotherapy drug efflux. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive choline magnesium trisalicylate orally (PO) every 8 hours on days 0-7, idarubicin intravenously (IV) on days 1-3, and cytarabine IV continuously on days 1-7. ARM II: Patients receive idarubicin IV on days 1-3 and cytarabine IV continuously on days 1-7. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Official Title
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A Randomized Phase II Study of Nuclear Factor-kappa B (NF-κB) Inhibition During Induction Chemotherapy for Patients With Acute Myelogenous Leukemia

Conditions
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Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: choline magnesium trisalicylate
* Drug: idarubicin
* Drug: cytarabine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of non-M3 AML (patients with M3 subtype are excluded); determination of the presence of cytogenetic abnormalities will be by standard cytogenetics +/- fluorescent-in-situ (FISH) studies; additional molecular analyses for nucleophosmin (NPM) mutation and fms-related tyrosine kinase 3 (flt3) internal tandem duplication will be obtained as a part of standard care by institutional procedures Leukemic blast count > 1500/mm^3 of peripheral blood Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 3 Total bilirubin < 2 times the institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 3 times the institutional ULN Serum creatinine < 1.5 times the institutional ULN Multi gated acquisition scan (MUGA) or echocardiogram with left ventricular ejection fraction (LVEF) > 50% Women of childbearing potential must have a negative pregnancy test No uncontrolled psychiatric illness that the principal investigator feels will compromise obtaining informed consent from a patient Patient must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines; patients who do not provide informed consent will not be eligible for the study Exclusion Criteria: Any coexisting medical condition or medications precluding full compliance with any of the arms of the study Allergies to any investigational drugs and/or to the chemotherapeutic agents Allergies to any non-steroidal anti-inflammatory drugs (NSAIDs)/salicylates (e.g., aspirin) Endoscopically documented upper or lower gastrointestinal (GI) related hemorrhage within last 6 months; also, patients with a clinical diagnosis of GI bleeding requiring blood transfusions will be excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (choline magnesium trisalicylate and chemotherapy)<br>Patients receive choline magnesium trisalicylate PO every 8 hours on days 0-7, idarubicin IV on days 1-3, and cytarabine IV continuously on days 1-7. | Drug: choline magnesium trisalicylate<br>* Given PO<br>* Other names: Trisalicylate;Drug: idarubicin<br>* Given IV<br>* Other names: IDA;Drug: cytarabine<br>* Given IV<br>* Other names: cytosine arabinoside;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Active Comparator: Arm II (chemotherapy)<br>Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7. | Drug: idarubicin<br>* Given IV<br>* Other names: IDA;Drug: cytarabine<br>* Given IV<br>* Other names: cytosine arabinoside;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of NF-kB Target Transcripts and/or Inhibition of Drug Efflux in at Least 50% of Patients | The clinical trial will be based on a sequential monitoring so that we will have a 90% confidence that choline magnesium trisalicylate (CMT) based modulation of NF-kB transcriptional targets and/or drug efflux occurs in at least 50% of patients. | 24 hours |