Matched Targeted Therapy For High-Risk Leukemias and MDS

This study will determine whether it is possible to use profiling results and 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.

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 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.

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, first or greater relapse

- Acute myeloid leukemia, 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, new diagnosis

- New diagnosis infant MLL-rearranged ALL or low hypodiploid (<40 chromosomes) ALL

- Rare leukemia- e.g., 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.