Gene Expression During Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Treated With Choline Magnesium Trisalicylate

Study Overview
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Brief Summary
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RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in cancer cells. It may also help doctors understand how cancer cells respond to treatment with choline magnesium trisalicylate. PURPOSE: This pilot clinical trial is studying gene expression in cancer cells during chemotherapy and the safety of choline magnesium trisalicylate in treating patients with newly diagnosed acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Primary Determine temporal changes in leukemic cell NF-kB activity when choline magnesium trisalicylate is administered during induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Determine toxicities of this regimen in these patients. Secondary Determine patterns of leukemic cell gene expression in patients treated with this regimen. Determine if NF-kB modulation results in enhanced apoptosis in patients treated with this regimen. OUTLINE: This is an open-label, pilot study. Patients receive oral choline magnesium trisalicylate every 8 hours for 48 hours or dexamethasone every 6 hours for 48 hours plus choline magnesium trisalicylate every 8 hours for 48 hours during induction chemotherapy as determined by the primary physician. Blood is collected at baseline, 24 hours, and 48 hours to assess for changes in NF-kB expression, apoptosis, and gene expression in leukemic cells. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Official Title
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A Pilot Study of Nuclear Factor-kappa B (NFkB) Inhibition During Induction Chemotherapy for Patients With Acute Myelogenous Leukemia (AML)

Conditions
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Leukemia

Intervention / Treatment
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* Drug: choline magnesium trisalicylate
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed acute myeloid leukemia Newly diagnosed disease Presence of cytogenetic abnormalities must be determined by standard cytogenetics with or without FISH studies Leukemic blast count > 5,000/mm³ of peripheral blood No acute promyelocytic leukemia (M3) PATIENT CHARACTERISTICS: ECOG performance status 0-3 Bilirubin < 2.0 times upper limit of normal (ULN) AST < 3.0 times ULN Creatinine < 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled psychiatric illness that, in the opinion of the principal investigator, would preclude study compliance No other concurrent medical condition that would preclude study compliance No allergies to any investigational drugs and/or chemotherapeutic agents No upper or lower gastrointestinal (GI) related hemorrhage within the past 6 months as determined by endoscopy No clinical diagnosis of GI bleeding requiring blood transfusions PRIOR CONCURRENT THERAPY: No prior induction therapy No prior chemotherapy for acute leukemia No concurrent medications that would preclude study compliance

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone plus Choline Magnesium Trisalicylate<br>Dexamethasone plus Choline Magnesium Trisalicylate | Drug: choline magnesium trisalicylate<br>* 1500mg orally every 8 hours beginning at hour 0 and continuing until hour 48.<br>Drug: Dexamethasone<br>* 10mg orally every 6 hours beginning at hour 0 and continuing until hour 48.<br>|
| Experimental: Choline Magnesium Trisalicylate<br>Choline Magnesium Trisalicylate | Drug: choline magnesium trisalicylate<br>* 1500mg orally every 8 hours beginning at hour 0 and continuing until hour 48.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temporal changes in leukemic cell NF-kB activity |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patterns of leukemic cell gene expression after administration of choline magnesium trisalicylate |  | 5 years | 
| Apoptosis related to NF-kB modulation |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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 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