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

NCT ID: NCT02144675

Last Updated: 2021-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2016-04-26

Brief Summary

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

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

choline magnesium trisalicylate

Intervention Type: DRUG

Given PO

idarubicin

Intervention Type: DRUG

Given IV

cytarabine

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm II (chemotherapy)

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

Group Type: ACTIVE_COMPARATOR

idarubicin

Intervention Type: DRUG

Given IV

cytarabine

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

choline magnesium trisalicylate

Given PO

Intervention Type: DRUG

idarubicin

Given IV

Intervention Type: DRUG

cytarabine

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Trilisate; Trisalicylate; 4-demethoxydaunorubicin; 4-DMDR; DMDR; IDA; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rutgers Cancer Institute of New Jersey

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: lead

Responsible Party

Roger Strair, MD, PhD

Professor of Medicine, RWJMS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roger Strair

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Countries

United States

Other Identifiers

NCI-2012-00516

Identifier Type: REGISTRY

Identifier Source: secondary_id

0220080282

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

020803

Identifier Type: OTHER

Identifier Source: secondary_id

0220080282

Identifier Type: -

Identifier Source: org_study_id