Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia
Primary Purpose
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
choline magnesium trisalicylate
idarubicin
cytarabine
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Adult Acute Megakaryoblastic Leukemia (M7)
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
Sites / Locations
- Rutgers Cancer Institute of New Jersey
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm I (choline magnesium trisalicylate and chemotherapy)
Arm II (chemotherapy)
Arm 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.
Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02144675
First Posted
May 20, 2014
Last Updated
August 20, 2021
Sponsor
Rutgers, The State University of New Jersey
Collaborators
Rutgers Cancer Institute of New Jersey, National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02144675
Brief Title
Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia
Official Title
A Randomized Phase II Study of Nuclear Factor-kappa B (NF-κB) Inhibition During Induction Chemotherapy for Patients With Acute Myelogenous Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
April 26, 2016 (Actual)
Study Completion Date
April 26, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
Rutgers Cancer Institute of New Jersey, National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (choline magnesium trisalicylate and chemotherapy)
Arm Type
Experimental
Arm 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.
Arm Title
Arm II (chemotherapy)
Arm Type
Active Comparator
Arm Description
Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7.
Intervention Type
Drug
Intervention Name(s)
choline magnesium trisalicylate
Other Intervention Name(s)
Trilisate, Trisalicylate
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
idarubicin
Other Intervention Name(s)
4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Inhibition of NF-kB Target Transcripts and/or Inhibition of Drug Efflux in at Least 50% of Patients
Description
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.
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger Strair
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia
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