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

• Sponsor: Rutgers, The State University of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT02144675
• Collaborator: Rutgers Cancer Institute of New Jersey (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 27
• Location: 1
• Arms: 2
• Duration (Months): 87.8
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: choline magnesium trisalicylate; Drug: idarubicin; Drug: cytarabine; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. To determine toxicities associated with administration of salicylate in the setting of induction chemotherapy.

3. To determine if salicylate alters the expression of NF-kB-regulated genes in AML cells.

4. 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 Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jan 1, 2009
• Actual Primary Completion Date: Apr 26, 2016
• Actual Study Completion Date: Apr 26, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Inhibition of NF-kB Target Transcripts and/or Inhibition of Drug Efflux in at Least 50% of Patients [24 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903

Sponsors and Collaborators

• Rutgers, The State University of New Jersey
• Rutgers Cancer Institute of New Jersey
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Roger Strair, Rutgers Cancer Institute of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roger Strair, MD, PhD, Professor of Medicine, RWJMS, Rutgers Cancer Institute of New Jersey
• ClinicalTrials.gov Identifier: NCT02144675
• Other Study ID Numbers: 0220080282; NCI-2012-00516; 0220080282; P30CA072720; 020803
• First Posted: May 22, 2014
• Last Update Posted: Aug 24, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Cytarabine; Choline magnesium trisalicylate; Salicylates; Idarubicin; Choline

Study Results

Participant Flow

Recruitment Details	Subjects were recruited through the Rutgers Cancer Institute of New Jersey. The study was open to accrual on 10/31/2008 and completed on 01/06/2015. All participants visits were completed and the study was closed by the Principal Investigator on 04/26/2016.

Arm/Group Title	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)	Arm II (Chemotherapy)
Arm/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. choline magnesium trisalicylate: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies	Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7. idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	13	14
COMPLETED	13	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)	Arm II (Chemotherapy)	Total
Arm/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. choline magnesium trisalicylate: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies	Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7. idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	13	14	27
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 76.9%	9 64.3%	19 70.4%
>=65 years	3 23.1%	5 35.7%	8 29.6%
Sex: Female, Male (Count of Participants)
Female	6 46.2%	10 71.4%	16 59.3%
Male	7 53.8%	4 28.6%	11 40.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%	0 0%	1 3.7%
Not Hispanic or Latino	12 92.3%	14 100%	26 96.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 7.1%	1 3.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 15.4%	0 0%	2 7.4%
White	11 84.6%	13 92.9%	24 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	13 100%	14 100%	27 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)	Arm II (Chemotherapy)
Arm/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. choline magnesium trisalicylate: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies	Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7. idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	13	14
Count of Participants [Participants]	13 100%	14 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Choline Magnesium Trisalicylate and Chemotherapy), Arm II (Chemotherapy)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	Regression, Cox
	Comments

Adverse Events

Time Frame	Adverse events were collected over a period of approximately 1.5 months.
Arm/Group Title	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)		Arm II (Chemotherapy)
Arm/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. choline magnesium trisalicylate: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies		Patients receive idarubicin IV on days 1- 3 and cytarabine IV continuously on days 1-7. idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)		Arm II (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/14 (0%)
Serious Adverse Events
	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)		Arm II (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates	1/13 (7.7%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm I (Choline Magnesium Trisalicylate and Chemotherapy)		Arm II (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/13 (53.8%)		10/14 (71.4%)
Blood and lymphatic system disorders
Alkalosis (metabolic or respiratory)	1/13 (7.7%)	1	0/14 (0%)	0
Dermal change lymphedema, phlebolymphedema	1/13 (7.7%)	1	0/14 (0%)	0
Low Platelets	2/13 (15.4%)	2	2/14 (14.3%)	2
Low Hemoglobin	3/13 (23.1%)	3	3/14 (21.4%)	3
Neutropenia	1/13 (7.7%)	1	0/14 (0%)	0
Neutrophils/granulocytes (ANC/AGC)	0/13 (0%)	0	1/14 (7.1%)	1
Gastrointestinal disorders
Constipation	1/13 (7.7%)	1	0/14 (0%)	0
Colitis	1/13 (7.7%)	1	0/14 (0%)	0
Diarrhea	1/13 (7.7%)	1	2/14 (14.3%)	2
Nausea	0/13 (0%)	0	2/14 (14.3%)	2
Mucositis/stomatitis (clinical exam) - Oral cavity	0/13 (0%)	0	1/14 (7.1%)	1
Heartburn/dyspepsia	0/13 (0%)	0	1/14 (7.1%)	1
Enteritis (inflammation of the small bowel)	0/13 (0%)	0	1/14 (7.1%)	1
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	0/13 (0%)	0	1/14 (7.1%)	1
General disorders
Glucose, serum-high (hyperglycemia)	1/13 (7.7%)	1	0/14 (0%)	0
Potassium, serum-low (hypokalemia)	1/13 (7.7%)	1	0/14 (0%)	0
Calcium, serum-low (hypocalcemia)	1/13 (7.7%)	1	0/14 (0%)	0
Pain - Abdomen NOS	0/13 (0%)	0	1/14 (7.1%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	0/13 (0%)	0	2/14 (14.3%)	2
Pain - Head/headache	0/13 (0%)	0	1/14 (7.1%)	1
Pain - Sore Throat	0/13 (0%)	0	1/14 (7.1%)	1
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/13 (7.7%)	1	0/14 (0%)	0
Infections and infestations
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	1/13 (7.7%)	1	4/14 (28.6%)	4
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	1/13 (7.7%)	1	0/14 (0%)	0
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e	0/13 (0%)	0	1/14 (7.1%)	1
Renal and urinary disorders
Cystitis	0/13 (0%)	0	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/13 (0%)	0	1/14 (7.1%)	1
Dyspnea (shortness of breath)	0/13 (0%)	0	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Rash	1/13 (7.7%)	1	3/14 (21.4%)	3
Vascular disorders
Hypotension	0/13 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.