Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: December 2, 2010
Last updated: March 5, 2015
Last verified: January 2015
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.

Condition Intervention Phase
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
Drug: Daunorubicin Hydrochloride
Drug: Sorafenib Tosylate
Drug: Cytarabine
Procedure: Bone Marrow Aspiration
Procedure: Biopsy
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (OS) rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of patients who were alive at 1 year. The 1-year OS was estimated using the Kaplan Meier method.

Secondary Outcome Measures:
  • OS [ Time Frame: Time from registration to death (up to 10 years) ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.

  • Event-free survival [ Time Frame: Time from registration to death or relapse (up to 10 years) ] [ Designated as safety issue: No ]
    Event-free survival (EFS) was defined as the time for registration to failure to achieve CR during induction, relapse or death. Participants without events were censored at date of last follow-up. The median EFS with 95% CI was estimated using the Kaplan Meier method.

Enrollment: 54
Study Start Date: April 2011
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (daunorubicin, cytarabine, sorafenib tosylate)

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.

Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
  • DNM
  • DNR
  • DRB
Drug: Sorafenib Tosylate
Given PO
Other Names:
  • BAY 54-9085
  • Nexavar
  • SFN
Drug: Cytarabine
Given IV
Other Names:
  • CHX-3311
  • U-19920
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspirate
Procedure: Biopsy
Undergo biopsy
Other Name: Bx
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies

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Detailed Description:


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.


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.


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.


Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01253070

  Show 43 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Geoffrey Uy Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT01253070     History of Changes
Other Study ID Numbers: NCI-2011-02618  NCI-2011-02618  CDR0000689593  CALGB 11001  CALGB-11001  U10CA180821  U10CA031946 
Study First Received: December 2, 2010
Last Updated: March 5, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
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