This trial is active, not recruiting.

Conditions acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13;q13); rbm15-mkl1, acute myeloid leukemia with a variant rara translocation, acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); rpn1-evi1, acute myeloid leukemia with t(6;9)(p23;q34); dek-nup214, acute myeloid leukemia with t(9;11)(p22;q23); mllt3-mll, acute myeloid leukemia with variant mll translocations, untreated adult acute myeloid leukemia
Treatments daunorubicin hydrochloride, sorafenib tosylate, cytarabine, bone marrow aspiration, biopsy, laboratory biomarker analysis, quality-of-life assessment, questionnaire administration
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date April 2011
End date October 2014
Trial size 54 participants
Trial identifier NCT01253070, CALGB 11001, CALGB-11001, CDR0000689593, NCI-2011-02618, U10CA031946, U10CA180821


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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 400mg 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.
daunorubicin hydrochloride DNM
Given IV
sorafenib tosylate BAY 54-9085
Given PO
cytarabine CHX-3311
Given IV
bone marrow aspiration
Undergo bone marrow aspirate
biopsy Bx
Undergo biopsy
laboratory biomarker analysis
Correlative studies
quality-of-life assessment Quality of Life Assessment
Ancillary studies
questionnaire administration
Ancillary studies

Primary Outcomes

Overall Survival (OS) Rate
time frame: 1 year

Secondary Outcomes

time frame: Time from registration to death (up to 10 years)
Event-free Survival
time frame: Time from registration to death or relapse (up to 10 years)

Eligibility Criteria

Male or female participants at least 60 years old.

Inclusion Criteria: - Unequivocal histologic diagnosis of AML according to World Health Organization (WHO) criteria, EXCLUDING: - Acute promyelocytic leukemia t(15;17)(q22;q12); promyelocytic leukemia (PML)-retinoic acid receptor, alpha (RARA) - Acute myeloid leukemia with t(8;21)(q22;q22); runt-related transcription factor 1 (RUNX1-RUNXT1) as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per Cancer and Leukemia Group B (CALGB) 20202 - Acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16(p13.1;q22); core-binding factor, beta subunit (CBFB)-myosin, heavy chain 11, smooth muscle (MYH11) as determined by the OSU Molecular Reference Laboratory, per CALGB 20202 - AML patients with an antecedent hematologic disorder are eligible for treatment on this trial provided that they have not received chemotherapy, including lenalidomide, azacitidine or decitabine for their hematologic disorder - Patients with therapy-related AML are eligible if there had been no further exposure to chemotherapy or radiation therapy for > 3 years and their primary malignancy is in remission - FLT3 mutation (ITD or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202 - No prior chemotherapy for AML with the following exceptions: - Emergency leukapheresis - Emergency treatment for hyperleukocytosis with hydroxyurea - Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only) - Growth factor/cytokine support - All-trans retinoic acid (ATRA)

Additional Information

Official title A Phase II Study Incorporating Sorafenib (NSC 724772) Into the Therapy of Patients ≥ 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia
Principal investigator Geoffrey Uy
Description PRIMARY OBJECTIVES: I. To determine if the 1-year overall survival rate of patients age >= 60 with fms-related tyrosine kinase 3 (FLT3)-internal-tandem duplications (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. VI. To describe the interaction of FLT3 mutation type (tyrosine kinase domain [TKD] vs. ITD) and allelic ratio on clinical outcomes. 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. 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. IX. To explore the impact of induction chemotherapy on physical, cognitive, psychosocial factors. 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 courses 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 courses 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 courses 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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).