Matched Targeted Therapy For High-Risk Leukemias and Myelodysplastic Syndrome

NCT ID: NCT02670525

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 338 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-17
• Study Completion Date: 2028-01-31

Brief Summary

This research study is seeking to gain new knowledge about Recurrent, Refractory, or High Risk Leukemias in children and young adults.

This study is evaluating the use of specialized testing called leukemia profiling. Once the profiling is performed, the results are evaluated by an expert panel of physicians, scientists and pharmacists. This may result in a recommendation for a specific cancer therapy or a clinical trial called matched targeted therapy (MTT). The results of the leukemia profiling and, if applicable, the MTT recommendation will be communicated to the participant's primary oncologist.

Detailed Description

Our tissues and organs are made up of cells. Cancer occurs when the molecules that normally control cell growth are damaged. The damage results in unchecked cell growth which causes a tumor, a collection of cancer cells. The damage is referred to as an alteration. There are different types of cancer-causing alterations. Genes are the part of cells that contain the instructions which tell our cells how to make the right proteins to grow and work. Genes are composed of Deoxyribonucleic Acid (DNA) letters that spell out these instructions.

By participating in this study, the participant's leukemia cells will be tested for cancer causing alterations. This testing is called leukemia profiling. The leukemia profiling will be performed using bone marrow or blood that has already been obtained during a clinical test. Alternately, the profiling may be done on leukemia cells that are planned to be obtained as part of routine clinical care.

This study will determine whether it is possible to use profiling results to determine a matched targeted therapy for patients with leukemia. It will describe the range of mutations found in patients with leukemia with this type of profiling, and describe the clinical outcomes of patients who receive a matched targeted therapy.

Conditions

Recurrent, Refractory, or High Risk Leukemias; Matched Targeted Therapy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Relapsed/Refractory Leukemia

Cohort 1: Relapsed/Refractory Leukemia

• Acute lymphoblastic leukemia (ALL), first or greater relapse
• Acute myeloid leukemia (AML), first or greater relapse
• Leukemia refractory to induction chemotherapy
• Other recurrent leukemia
• Myelodysplastic syndrome (MDS), first or greater relapse, or refractory to initial therapy

After the screening procedures confirms patient eligibility:

• Leukemia Profiling will be performed
• Identifying an actionable genomic alteration and making a matched targeted therapy treatment recommendation.

Group Type: EXPERIMENTAL

Leukemia Profiling

Intervention Type: GENETIC

Genetic profiling of leukemia cells will be performed and analyzed by an expert panel. Matched targeted therapy recommendation based on profiling results will be made if available. The recommendation, if available, will be communicated to the primary oncologist.

New Diagnosis

Cohort 2: New Diagnosis

• Acute myeloid leukemia (AML), new diagnosis (excluding acute promyelocytic leukemia (APL))
• New diagnosis infant mixed-lineage leukemia (MLL)-rearranged ALL or low hypodiploid (<40 chromosomes) ALL
• Rare leukemia- e.g., juvenile myelomonocytic leukemia (JMML), leukemia of ambiguous lineage
• Secondary leukemia
• Myelodysplastic syndrome (MDS) not eligible for stem cell transplant

After the screening procedures confirms eligibility:

• Leukemia Profiling will be performed
• Identifying an actionable genomic alteration and making a matched targeted therapy treatment recommendation.

Group Type: EXPERIMENTAL

Leukemia Profiling

Intervention Type: GENETIC

Genetic profiling of leukemia cells will be performed and analyzed by an expert panel. Matched targeted therapy recommendation based on profiling results will be made if available. The recommendation, if available, will be communicated to the primary oncologist.

Interventions

Leukemia Profiling

Genetic profiling of leukemia cells will be performed and analyzed by an expert panel. Matched targeted therapy recommendation based on profiling results will be made if available. The recommendation, if available, will be communicated to the primary oncologist.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Birth to ≤ 30 years at study entry
• Diagnosis: Patients will be enrolled in one of the two cohorts based on diagnosis:

Cohort 1: Relapsed/refractory leukemia

• Acute lymphoblastic leukemia (ALL), first or greater relapse
• Acute myeloid leukemia (AML), first or greater relapse
• Leukemia refractory to induction chemotherapy
• Other recurrent leukemia
• Myelodysplastic syndrome (MDS), first or greater relapse, or refractory to initial therapy

Cohort 2: New diagnosis

• Acute myeloid leukemia (AML), new diagnosis
• New diagnosis infant mixed-lineage leukemia (MLL)-rearranged ALL or low hypodiploid (<40 chromosomes) ALL
• Rare leukemia- e.g., juvenile myelomonocytic leukemia (JMML), leukemia of ambiguous lineage
• Secondary leukemia
• Myelodysplastic syndrome (MDS) not eligible for stem cell transplant

Pathologic Criteria

• Histologic confirmation of leukemia at the time of diagnosis or recurrence

Specimen Samples

• Sufficient leukemia specimen available for profiling from diagnosis or recurrence OR bone marrow aspirate/blood draw/pheresis/other fresh sample of patient leukemia cells planned for clinical care anticipated to allow collection of minimum specimen for testing.

Exclusion Criteria

• Insufficient leukemia specimen available for profiling from diagnosis or recurrence; or bone marrow evaluation/blood draw/other leukemia cell sample NOT planned to be obtained for clinical care; or peripheral blast percentage <20% AND clinical blood draw not planned.

• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Yana Pikman, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yana Pikman, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

The University of Chicago

Chicago, Illinois, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Children's Hospital's and Clinics of Minnesota

Minneapolis, Minnesota, United States

Washington University at St. Louis School of Medicine

St Louis, Missouri, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

The Children's Hospital at Montefiore

The Bronx, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Seattle Children's Hospital

Seattle, Washington, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Paolino J, Dimitrov B, Apsel Winger B, Sandoval-Perez A, Rangarajan AV, Ocasio-Martinez N, Tsai HK, Li Y, Robichaud AL, Khalid D, Hatton C, Gillani R, Polonen P, Dilig A, Gotti G, Kavanagh J, Adhav AA, Gow S, Tsai J, Li Y, Ebert BL, Van Allen EM, Bledsoe J, Kim AS, Tasian SK, Cooper SL, Cooper TM, Hijiya N, Sulis ML, Shukla NN, Magee JA, Mullighan CG, Burke MJ, Luskin MR, Mar BG, Jacobson MP, Harris MH, Stegmaier K, Place AE, Pikman Y. Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma. Clin Cancer Res. 2023 Nov 14;29(22):4613-4626. doi: 10.1158/1078-0432.CCR-22-2562.

Reference Type: DERIVED

PMID: 37725576 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15-384

Identifier Type: -

Identifier Source: org_study_id