S9031-S9333-S0112-S0301-A Biomarkers Associated With Response to Cytarabine in Samples From Older Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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RATIONALE: Studying samples of blood and tissue from patients with cancer treated with cytarabine in the laboratory may help doctors learn more about the effects of cytarabine on cells. It may also help doctors understand how well patients respond to treatment. PURPOSE: This research trial studies biomarkers associated with response to cytarabine in samples from older patients with acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Refinement and testing of a multiparameter flow cytometry-based cell-signaling signature (FC classifier) associated with in vivo likelihood of complete response (CR) to cytarabine-based induction chemotherapy in elderly patients (56 years and older) newly diagnosed with non-M3 acute myeloid leukemia (AML). Identification of cell-signaling signature(s) associated with continuous CR to cytarabine-based induction chemotherapy at one year (CCR1) in adult patients 56 years and older with a newly diagnosed non-M3 AML. Identification of cell-signaling signature(s) associated with relapse-free survival at one year (RFS1) in adult patients 56 years and older with a newly diagnosed non-M3 AML who received cytarabine-based induction chemotherapy and achieved CR. To investigate changes in cell-signaling signature(s) between matched pre- and post-treatment specimens of relapsed/refractory patients. OUTLINE: This is a multicenter study. Cryopreserved specimens are incubated with cytokines (e.g., interleukins), growth factors (e.g., sargramostim or filgrastim), and chemotherapeutic agent (e.g., cytarabine, etoposide) and other modulators. Cells are then fixed, permeabilized, and stained with antibodies that recognize extracellular markers (for example, surface phenotypic markers such as clusters of differentiation, drug transporters, and receptors) in conjunction with intracellular activation-state-specific epitopes of designated signaling molecules. Subsequently, cell are analyzed by phospho-flow cytometry (FC) in a random manner (without knowledge of clinical variables and outcomes) to a training set (complete pre-specified FC) versus a testing set. Cells are also analyzed by proteomic assays. Results are then compared with individual patient scores, including predicted clinical outcomes.

Official Title
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Proteomic Signature Associated With Clinical Response to Cytarabine Based Induction Therapy in Patients With AML 56 Years and Older

Conditions
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Leukemia

Intervention / Treatment
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* Genetic: gene expression analysis
* Genetic: proteomic profiling
* Other: flow cytometry
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Newly diagnosed with non-M3 acute myeloid leukemia (AML) Pretreatment and relapse/refractory cryopreserved marrow and circulating mononuclear cells (MC) from patients who meet the following criteria: Eligible and evaluable patients on study SWOG-9031, SWOG-9333 (Ara-C/DNR induction arm only), SWOG-S0112, or SWOG-S0301 Did not refuse consent for this use of specimens Have 2+ vials of pretreatment marrow cells and/or 2+ vials of pretreatment peripheral blood cells in the Southwest Oncology Group (SWOG) AML/MDS Repository PATIENT CHARACTERISTICS: See Disease Characteristics PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 56 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: gene expression analysis|nan|
|Genetic: proteomic profiling|nan|
|Other: flow cytometry|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to induction chemotherapy: complete response (CR) vs non-complete response (NR) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete continuous response at one year (CCR1) |  | 1 year | 
| Relapse-free survival at one year (RFS1) |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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), recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7)