S0106A, Biomarkers in Samples From Patients With Newly Diagnosed Acute Myeloid Leukemia Treated With Cytarabine-Based Chemotherapy

S0106A, Proteomic Signatures Associated With Complete Response (CR) and Complete Continuous Response at One Year (CCR1) Following Cytarabine-Based Induction Chemotherapy in Younger Adult Patients (18-60 Years of Age) With a Newly Diagnosed Non-M3 AML

RATIONALE: Studying samples of bone marrow and blood from patients with cancer in the laboratory may help doctors predict how well patients will respond to treatment.

PURPOSE: This research study studies biomarkers in samples from patients with newly diagnosed acute myeloid leukemia treated with cytarabine-based chemotherapy.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Other: laboratory biomarker analysis; Genetic: proteomic profiling; Other: flow cytometry

Detailed Description

OBJECTIVES:

• Training and testing of multiparameter flow cytometry-based cell signaling signature (FC classifier 1) associated with in vivo primary chemoresistance (i.e., non-complete response [NR]) to standard induction therapy in adult patients ≤ 60 years old with a newly diagnosed non-M3 acute myeloid leukemia (AML).
• Training and testing of multiparameter flow cytometry-based cell signaling signature (FC classifier 2) associated with complete continuous response at 1 year (CCR1) in adult patients ≤ 60 years old with a newly diagnosed non-M3 AML who are treated with cytarabine-based induction chemotherapy.
• Identification of signaling signature(s) associated with secondary chemoresistance (i.e., disease relapse) in adult patients ≤ 60 years of age who have longitudinally paired peripheral blood mononuclear cells (PBMC) or bone marrow mononuclear cells (BMMC) samples at diagnosis and at the time of first relapse. (Exploratory)

OUTLINE: Cryopreserved samples are incubated with cytokines (e.g., interleukins), growth factors (e.g., sargramostim [GM-CSF] and filgrastim [G-CSF]), chemotherapeutic agents (e.g., cytarabine, etoposide phosphate), and other modulators. Cells are fixed, permeabilized, and stained with antibodies that recognize extracellular markers in conjunction with intracellular activation-state specific epitopes of designated signaling molecules. Subsequently, cells are analyzed for multiparametric phospho-flow cytometry in a random manner (without knowledge of clinical variables and outcomes) to training and testing sets. Results are then compared with individual patient clinical outcomes.

• Study Type: Observational
• Enrollment (Actual): 310

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients enrolled in S0106 that consented to use of specimens for future reserach

Description

DISEASE CHARACTERISTICS:

• Newly diagnosed non-M3 acute myeloid leukemia (AML)
• Pretreatment and relapsed and/or refractory cryopreserved bone marrow mononuclear cells (BMMCs) and peripheral blood mononuclear cells (PBMCs) available

• Have 2+ vials of pretreatment marrow cells and/or 2+ vials of pretreatment PBMCs in the Southwestern Oncology Group (SWOG) AML/Myelodysplastic Syndrome (MDS) Repository

  • Usable samples must contain approximately 1.6 ×10^6 cluster of differentiation antigen 45+ (CD45+) cells post thaw.
• Eligible and evaluable patients who participated on SWOG-S0106 study

PATIENT CHARACTERISTICS:

• Did not refuse consent for this use of specimens

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response to induction chemotherapy (complete response vs non-complete response) (classifier 1)	immediate
CCR1 at 1 year (classifier 2)	immediate

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jerry Radich, MD, Fred Hutchinson Cancer Center

Publications and helpful links

General Publications

• Medeiros BC, Othus M, Fang M, Appelbaum FR, Erba HP. Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia. Haematologica. 2015 Mar;100(3):331-5. doi: 10.3324/haematol.2014.117267. Epub 2014 Dec 19.
• Medeiros BC, Othus M, Estey EH, Fang M, Appelbaum FR. Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia. Br J Haematol. 2014 Jan;164(2):245-50. doi: 10.1111/bjh.12625. Epub 2013 Oct 28.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 21, 2011
• First Submitted That Met QC Criteria: May 21, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Estimate): April 15, 2016
• Last Update Submitted That Met QC Criteria: April 14, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: 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 myeloid leukemia in remission; adult acute erythroid leukemia (M6); 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 myelomonocytic leukemia (M4); adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute myeloid leukemia with del(5q)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: S0106A (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract)