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

Rutgers The State University of New Jersey

Status and phase: Completed; Phase 2

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

Treatments: Drug: choline magnesium trisalicylate; Other: laboratory biomarker analysis; Drug: cytarabine; Drug: idarubicin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02144675

P30CA072720 (U.S. NIH Grant/Contract)

020803

0220080282 (Other Identifier)

NCI-2012-00516 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

27 participants in 2 patient groups

Arm I (choline magnesium trisalicylate and chemotherapy)

Experimental group

Description:

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.

Treatment:

Drug: idarubicin

Drug: cytarabine

Other: laboratory biomarker analysis

Drug: choline magnesium trisalicylate

Arm II (chemotherapy)

Active Comparator group

Description:

Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7.

Treatment:

Drug: idarubicin

Drug: cytarabine

Other: laboratory biomarker analysis