Clinical trial NCT01360125: S0106A, Biomarkers in Samples From Patients With Newly Diagnosed Acute Myeloid Leukemia Treated With Cytarabine-Based Chemotherapy
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukemia
Keywords: adult acute basophilic leukemia
adult acute eosinophilic leukemia
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 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)
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-05-25
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients enrolled in S0106 that consented to use of specimens for future reserach

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response to induction chemotherapy (complete response vs non-complete response) (classifier 1)
timeFrame: immediate
measure: CCR1 at 1 year (classifier 2)
timeFrame: immediate
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Jerry Radich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.