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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Adult Acute Myeloid Leukemia; 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 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); Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia in Remission
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cytarabine; Drug: idarubicin; Drug: choline magnesium trisalicylate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (choline magnesium trisalicylate and chemotherapy); 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.	Other: laboratory biomarker analysis; Correlative studies; Drug: cytarabine; Given IV; Other Names: Cytosar-U; cytosine arabinoside; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Drug: idarubicin; Given IV; Other Names: IDA; 4-demethoxydaunorubicin; 4-DMDR; DMDR; Drug: choline magnesium trisalicylate; Given PO; Other Names: Trilisate; Trisalicylate
Active Comparator: Arm II (chemotherapy); Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7.	Other: laboratory biomarker analysis; Correlative studies; Drug: cytarabine; Given IV; Other Names: Cytosar-U; cytosine arabinoside; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Drug: idarubicin; Given IV; Other Names: IDA; 4-demethoxydaunorubicin; 4-DMDR; DMDR

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): April 26, 2016
• Study Completion (Actual): April 26, 2016

Study Registration Dates

• First Submitted: May 20, 2014
• First Submitted That Met QC Criteria: May 20, 2014
• First Posted (Estimate): May 22, 2014

Study Record Updates

• Last Update Posted (Actual): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Hypolipidemic Agents; Lipid Regulating Agents; Antibiotics, Antineoplastic; Nootropic Agents; Lipotropic Agents; Cytarabine; Idarubicin; Choline; Salicylates; Choline magnesium trisalicylate
• Other Study ID Numbers: 0220080282 (Other Identifier: IRB number); P30CA072720 (U.S. NIH Grant/Contract); NCI-2012-00516 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 020803 (Other Identifier: Rutgers Cancer Institute of New Jersey)