Clinical trial NCT01253070
Conditions: Acute Myeloid Leukemia With FLT3/ITD Mutation Acute Myeloid Leukemia With Inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1 Acute Promyelocytic Leukemia With PML-RARA FLT3 Gene Mutation Therapy-Related Acute Myeloid Leukemia
Sponsor: National Cancer Institute (NCI)
Start date: 2011-04-01; Completion date: 2021-04-15
Enrollment: 54 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II trial studies how well sorafenib tosylate and chemotherapy work in treating older patients with acute myeloid leukemia (AML). Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sorafenib tosylate and combination chemotherapy may be an effective treatment for AML.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine if the 1-year overall survival rate of patients age \>= 60 with FLT3-ITD AML treated with a sorafenib (sorafenib tosylate) containing induction and post-remission therapy is significantly higher than the historical 1-year overall survival rate of similar patients who were not treated with sorafenib.

SECONDARY OBJECTIVES:

I. To determine the rates of complete remission (CR), CR with incomplete count recovery (CRi), and cytogenetic complete remission (CCyR) to induction chemotherapy.

II. To determine the overall survival, event-free survival, and remission duration in patients treated on this study.

III. To describe the frequency and severity of adverse events for patients treated on this study.

IV. To describe the interaction of pre-treatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.

V. To assess FLT3 ligand concentrations and FLT3 plasma inhibitory activity during treatment and determine the relationship to clinical outcomes. (Cancer and Leukemia Group B \[CALGB\] 21003) VI. To describe the interaction of FLT3 mutation type (tyrosine kinase domain \[TKD\] vs. ITD) and allelic ratio on clinical outcomes. (CALGB 21003) VII. To characterize geriatric assessment measures in the context of a treatment trial for AML defined by: the observed distribution and number of missing values for each measurement. (CALGB 361006) VIII. To identify specific geriatric assessment measures which are independently associated with overall survival (OS), 30-day treatment-related mortality and key quality of life outcomes (number of days hospitalized, number of oncology clinic visits, admission to a nursing facility) in patients receiving induction chemotherapy for AML. (CALGB 361006) IX. To explore the impact of induction chemotherapy on physical, cognitive, psychosocial factors. (CALGB 361006)

OUTLINE:

INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously on days 1-7, and sorafenib tosylate orally (PO) twice daily (BID) on days 1-7. Patients then undergo a bone marrow aspirate or biopsy on day 14.

Patients with persistent disease undergo a second remission induction therapy comprising daunorubicin hydrochloride IV on days 1-2, cytarabine IV continuously on days 1-5, and sorafenib tosylate PO BID on days 1-7. Patients who achieve complete response (CR)\* proceed to consolidation therapy.

CONSOLIDATION THERAPY: Patients\*\* receive cytarabine IV over 3 hours on days 1-5 and sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with continued CR proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients who achieve CR and who are eligible for hematopoietic stem cell transplant (HSCT) are encouraged to enroll in Cancer and Leukemia Group B (CALGB) 100103. Patients in CR who are unable or unwilling to undergo HSCT receive two cycles of remission consolidation therapy.

NOTE: \*\* Patients in CR/complete remission with incomplete count recovery (CRi) who are unable or unwilling to complete remission consolidation therapy may proceed directly to maintenance therapy after consulting with the CALGB study chair.

After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then yearly for a maximum of 10 years.

Arms: arm 1: INDUCTION THERAPY: Daunorubicin hydrochloride 60 mg/m\^2/day by IV push or short IV on days 1-3, cytarabine 100 mg/m\^2/day by continuous IV on days 1-7, and sorafenib tosylate orally every 12 hours on days 1-7.

CONSOLIDATION THERAPY - Every 28 days for 2 cycles: Cytarabine 2 g/m\^2/day by IV on days 1-5 and sorafenib tosylate 400 mg orally every 12 hours on days 1-28.

MAINTENANCE - Every 28 days for up to 12 cycles: Sorafenib tosylate 400 mg orally every 12 hours on days 1-28.
Interventions: intervention 1: Biopsy intervention 2: Bone Marrow Aspiration intervention 3: Cytarabine intervention 4: Daunorubicin Hydrochloride intervention 5: Laboratory Biomarker Analysis intervention 6: Quality-of-Life Assessment intervention 7: Questionnaire Administration intervention 8: Sorafenib Tosylate
Intervention descriptions: intervention 1: Undergo biopsy intervention 2: Undergo bone marrow aspirate intervention 3: Given IV intervention 4: Given IV intervention 5: Correlative studies intervention 6: Ancillary studies intervention 7: Ancillary studies intervention 8: Given PO

Protocol documents: