Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title: A Phase Ib Feasibility Study of Personalized Kinase Inhibitor Therapy Combined With Induction in Acute Leukemias Who Exhibit In Vitro Kinase Inhibitor Sensitivity

Status Completed

Clinical Trial Summary

This phase IB trial studies the feasibility of using a functional laboratory based study to determine how well the test can be used to select personalized kinase inhibitor therapy in combination with standard chemotherapy in treating patients with newly diagnosed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It also evaluates safety and potential efficacy. Kinase inhibitor is a type of substance that blocks an enzyme called a kinase. Human cells have many different kinase enzymes, and they help control important cell functions. Certain kinases are more active in some types of cancer cells and blocking them may help keep the cancer cells from growing. Testing samples of blood from patients with AML and ALL in the laboratory with kinase inhibitors may help determine which kinase inhibitor has more activity against cancer cells and which one should be combined with standard of care chemotherapy. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving a personalized kinase inhibitor therapy combined with standard chemotherapy may be a better treatment for AML and ALL.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Determine feasibility of using an in vitro small molecule inhibitor screen to select kinase inhibitors to add to standard chemotherapy induction in AML or ALL.

SECONDARY OBJECTIVES:

I. Determine the safety and tolerability of the addition of the kinase inhibitors when added to standard chemotherapy induction.

II. Evaluate overall objective response rates at completion of induction therapy.

III. Evaluate need for re-induction at day 14 (+/- 3 days) for AML. IV. Evaluate sensitivity to kinase inhibitors using our in vitro small molecule inhibitor screen in newly diagnosed AML/ALL.

V. Determine twelve-month overall survival.

TERTIARY OBJECTIVES:

I. Perform next-generation mutational analysis in primary leukemia samples from study subjects at baseline to establish a panel of known mutations for each subject and at the time of bone marrow recovery after induction chemotherapy to measure residual disease and evaluate utility of next-generation sequencing as a method compared to flow cytometry for minimal residual disease (MRD).

II. Evaluate pharmacokinetics for each individual kinase inhibitor. III. Determine if there is a cytogenetic or other risk group that has a higher rate of treatment failure or inability to obtain results from the small molecule inhibitor screen.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (AML): Patients receive cytarabine intravenously (IV) continuously over 24 hours on days 1-7, and idarubicin IV over 30 minutes on days 1-3.

ARM II (ALL) CYCLE A: Patients receive cyclophosphamide IV over 3 hours twice daily (BID) on days 1-3, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV on day 4, dexamethasone PO on days 1-4 and 11-14, and rituximab IV on day 1 and 11 (day 11 only of course 1). Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II (ALL) CYCLE B: Patients receive cytarabine IV over 2 hours BID on days 2-3, methotrexate IV over 2-22 hours on day 1, methylprednisolone sodium succinate IV BID on days 1-3, leucovorin calcium IV every 6 hours until methotrexate level is < 0.05 uM and rituximab IV on days 1 and 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

In all arms, based on the results of the kinase inhibitor assay, patients receive either sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4-6 weeks, and then for a minimum of 1 year. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT02779283
• Study type: Interventional
• Source: OHSU Knight Cancer Institute
• Status: Completed
• Phase: Phase 1
• Start date: January 13, 2016
• Completion date: September 20, 2018