Study to Predict Risk of Relapse in Bone Marrow Cell Samples From Younger Patients With Acute Myeloid Leukemia

Validation of a Classifier for the Prediction of Risk of Relapse Using Single Cell Network Profiling (SCNP) Assays for Childhood AML

RATIONALE: A screening test, such as My Profile Pediatric Assay, may help doctors predict a patient's risk of relapse and plan better treatment for acute myeloid leukemia.

PURPOSE: This clinical trial is studying using the My Profile Pediatric Assay to see how well it works in predicting risk of relapse in bone marrow cell samples from younger patients with acute myeloid leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Other: diagnostic laboratory biomarker analysis

Detailed Description

OBJECTIVES:

Primary

• To validate the accuracy of the My Profile Pediatric Assay to predict risk of relapse in pediatric patients with non-M3 acute myeloid leukemia (AML) who responded to cytarabine-based induction chemotherapy.

Secondary

• To validate the continuous score from the pre-specified classifier as a predictor of relapse after response to induction chemotherapy, while controlling for the simultaneous effects of the following clinical and laboratory variables: age, WBC, ethnicity, cytogenetics, Flt3-ITD, NPM1, MRD, and bone marrow (BM) donor availability.
• To validate the accuracy of the prespecified low versus high relapse indicator variable (I_L/H) as a predictor of relapse after induction therapy.
• To validate the accuracy of the prespecified I_L/H as a predictor of relapse after induction therapy, while controlling for the simultaneous effects of the following clinical and laboratory variables: MRD, age, WBC, ethnicity, cytogenetics, Flt3-ITD, NPM1, and BM donor availability.

OUTLINE: Archived bone marrow mononuclear cells are analyzed by single cell network profile assay, the My Profile™ AML Risk of Relapse Assay. Molecular markers analyzed include Flt3-ITD, NPM1, and MRA. Results are then correlated with each patient's clinical data including patient's age, race/ethnic background, gender, treatment received, and outcomes.

• Study Type: Observational
• Enrollment (Anticipated): 98

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with confirmed non-M3 acute myeloid leukemia treated on COG-AAML03P1 or COG-AAML0531 protocols

Description

DISEASE CHARACTERISTICS:

• Patients with confirmed non-M3 acute myeloid leukemia

  • Treated on COG-AAML03P1 or COG- AAML0531 protocols

    • Samples from COG-AAML0531 can come from either treatment arm, but these samples need to be independent from any patients who donated samples assayed in study COG-AAML11B2
  • Patients with Down syndrome are excluded

• Cryopreserved bone marrow mononuclear cell (BMMC) samples collected at diagnosis, prior to start induction therapy

  • Samples must have been cryopreserved at central lab within 3 days of draw at clinical site
  • Target of 10 X 10^6 cells frozen
• Patients' clinical annotations required after unblinding

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Correlative studies; Archived bone marrow mononuclear cells are analyzed by single cell network proteomic profiling assay, the My Profile™ AML Risk of Relapse Assay. Molecular markers analyzed include Flt3-ITD, NPM1, and MRA. Results are then correlated with each patient's clinical data including patient's age, race/ethnic background, gender, treatment received, and outcomes.	Other: diagnostic laboratory biomarker analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the receiver operating characteristic (ROC) curve of continuous score from the pre-specified classifier in predicting relapse after complete response to cytarabine- based induction chemotherapy	A logistic regression model and area under the ROC curve for the model will be tested for significance against a null value of 0.5.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous score from the pre-specified classifier as a predictor of relapse after response to induction chemotherapy	A gate-keeper strategy will be applied to control the experiment-wise type I error rate at 0.05. The null hypothesis will be tested using a likelihood ratio test that will compare the likelihood for a full (LF) and a reduced (LR) logistic regression model of relapse (early relapse vs continuous complete response), where the full model will include the covariates and the continuous score from the pre-specified classifier and the reduced model will include only the covariates.	Up to 3 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Norman J. Lacayo, MD, Stanford University

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: September 17, 2011
• First Submitted That Met QC Criteria: September 17, 2011
• First Posted (Estimate): September 21, 2011

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: May 16, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; childhood acute erythroleukemia (M6); childhood acute megakaryocytic leukemia (M7); childhood acute minimally differentiated myeloid leukemia (M0); childhood acute basophilic leukemia; childhood acute eosinophilic leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies; childhood acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia with maturation (M2); childhood acute myelomonocytic leukemia (M4); childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: AAML11B12; CDR0000711851 (Other Identifier: Clinical Trials.gov); COG-AAML11B2 (Other Identifier: Children's Oncology Group); NCI-2011-03465 (Registry Identifier: CTRP (Clinical Trial Reporting Program))