Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

Clinical trial: A Phase 2 Study of Clofarabine, Idarubicin, Cytarabine, Vincristine, and Corticosteroids - Mixed Phenotype Acute Leukemia (MPAL)

Summary: The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, cytarabine, vincristine, and dexamethasone, with or without rituximab, can help to control mixed phenotype acute leukemia. The safety of this combination will also be studied.

Detailed description: Study Drug Administration:
  The study drugs will be given in what are called cycles. Each cycle is 28 days.
  Induction:
  The first cycle of study drugs is called Induction. If the doctor thinks it is needed, you will have up to 2 Induction cycles. During Induction cycles, you will receive:
  -  Clofarabine by vein over about 60 minutes on Days 1-4. If the doctor thinks it is in your best interest, you will only receive it on Days 1-3.
  -  Idarubicin by vein over about 30-60 minutes on Days 1-3, about 1-2 hours after you receive clofarabine. If the doctor thinks it is in your best interest, you will only receive it on Days 1 and 2.
  -  Cytarabine by vein over about 2 hours on Days 1-4, about 3-6 hours after you receive clofarabine.
  -  Vincristine by vein over about 15-30 minutes on Days 1, 8, and 15.
  -  Dexamethasone by vein over about 10-30 minutes on Days 1-4 and 15-18.
  -  If you have a certain type of leukemia and the doctor thinks it is in your best interest, you will also receive rituximab by vein over about 4-6 hours on Days 1 and 8. The study staff will tell you if you will receive rituximab.
  -  If you have a certain type of leukemia (AML FLT3-ITD) and the doctor thinks it is in your best interest, you may also receive sorafenib by mouth twice a day for 14 days.
  All patients will have at least one lumbar puncture (spinal tap) during the first cycle of induction. This is done to check the status of the disease and to give drugs to help prevent side effects, called intrathecal chemotherapy (methotrexate and/or cytarabine). Intrathecal chemotherapy is given by injecting the chemotherapy directly into the cerebrospinal fluid. The standard for patients is to receive 8 of these treatments. On this study, you will only receive the drug 1 time unless the study doctor thinks it is in your best interest to receive additional doses. Then you may receive it up to 8 times.
  If the doctor thinks it is in your best interest, your dose will be reduced after Induction.
  Consolidation:
  If the disease responds to the study drugs during Induction, you may receive up to 6 more cycles of study drugs. This is called Consolidation. During Consolidation cycles, you will receive:
  -  Clofarabine by vein over about 60 minutes on Days 1-3. If the doctor thinks it is in your best interest, you will only receive it on Days 1-2.
  -  Idarubicin by vein over about 30-60 minutes on Days 1-2, about 1-2 hours after you receive clofarabine.
  -  Cytarabine by vein over about 2 hours on Days 1-3, about 3-6 hours after you receive clofarabine. If the doctor thinks it is in your best interest, you will only receive it on Days 1 and 2.
  -  Vincristine by vein over about 15-30 minutes on Days 1, 8, and 15.
  -  Dexamethasone by vein over about 10-30 minutes on Days 1-4 and 15-18.
  -  If you have a certain type of leukemia and the doctor thinks it is in your best interest, you will also receive rituximab in Consolidation Cycles 1-3, by vein over about 4-6 hours on Days 1 and 8 . The study staff will tell you if you will receive rituximab.
  -  If you have a certain type of leukemia (AML FLT3-ITD) and the doctor thinks it is in your best interest, you may also receive sorafenib by mouth twice a day.
  Study Visits:
  Before each cycle, you will have a physical exam.
  Every 3-7 days, blood (about 2-3 teaspoons) will be drawn for routine tests.
  At the end of every cycle (+/- 7 days), you will have a bone marrow aspirate/biopsy collected to check the status of the disease and for cytogenetic testing.
  If the disease appears to get better, you will have these study visits less often. Blood will be drawn every 7-14 days, and you will only have a bone marrow aspirate/biopsy when the study doctor thinks it is needed.
  Length of Study:
  You may continue receiving the study drugs for 1-2 induction cycles and then up to 6 consolidation cycles. You will no longer be able to receive the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
  Your participation on the study will be over after you have completed the end-of-study visit, unless you will have maintenance treatment as discussed by you and the study doctor.
  End-of-Study Visit:
  You will have an end-of-study visit about 30 days after you stop receiving the study drugs. At this visit, the following tests and procedures will be performed:
  -  You will have a physical exam.
  -  Blood (about 2-3 teaspoons) will be drawn for routine tests.
  -  If the study doctor thinks it is needed, you will have a bone marrow aspirate and/or biopsy.
  -  If you can become pregnant, you will have a urine pregnancy test.
  This is an investigational study. Clofarabine is FDA approved and commercially available to treat acute lymphoblastic leukemia (ALL) in children. Idarubicin and cytarabine are FDA approved and commercially available to treat acute myeloid leukemia (AML). Rituximab is FDA approved and commercially available to treat various types of lymphoma and leukemia. The use of these drugs in combination with vincristine and dexamethasone to treat mixed phenotype acute leukemia is investigational.
  The study doctor can explain how the drugs are designed to work.
  Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.

Eligibility: Inclusion Criteria:
  1. Sign an informed consent document
  2. Age 18 to 80.
  3. Newly diagnosed or relapsed MPAL, which for this protocol, will be defined as follows: -Bone marrow result interpreted by the reading Pathologist (or tissue biopsy for cases of extramedullary disease) as: biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/Myeloid leukemia, B/Myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population.
  4. ECOG Performance Status of </= 3 at study entry.
  5. Adequate organ function as outlined below (unless due to leukemia), Serum creatinine </= 3 mg/dL, Total bilirubin </= 2.5 mg/dL, ALT (SGPT) and/or AST (SGOT) </= 3 x ULN or </= 5 x ULN if related to disease
  6. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days. Women of childbearing potential and men must agree to use contraception at study entry and for the duration of active study treatment.
  7. Cardiac ejection fraction >/= 40% (by either cardiac echo or MUGA scan). Documentation of recent (</= 6 months from screening) outside reports is acceptable.
  8. If newly diagnosed, prior therapy with hydrea and/or steroid and the use of a single or a two day dose of cytarabine (up to 3 g/m2), for emergency use up to 24 hours prior to start of study therapy is allowed.
  Exclusion Criteria:
  1. Breast feeding females
  2. Patients with active, uncontrolled infections
  3. Patients with active secondary malignancy will not be eligible unless approved by the Principal Investigator.

Relevance to patient case: not relevant