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

NCT01253070 | Completed Phase 2 Results

• 5 other identifiers: NCI-2011-02618CDR0000689593CALGB-11001U10CA180821U10CA031946
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 43

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) Rate

  Percentage of patients who were alive at 1 year. The analysis was split between patients with having a FLT3 (FMS-like tyrosine kinase-3) ITD (internal tandem duplication) or TKD (tyrosine kinase domain) mutation. The FLT3 mutation testing at baseline was performed centrally for all patients.

  1 year

Secondary Outcomes (2)

• OS

  Time from registration to death (up to 10 years)

• Event-free Survival

  Time from registration to death or relapse (up to 10 years)

Study Arms (1)

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

EXPERIMENTAL

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.

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

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspirate

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Questionnaire Administration OTHER

Ancillary studies

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Treatment (daunorubicin, cytarabine, sorafenib tosylate)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (43)

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Harold Alfond Center for Cancer Care

Augusta, Maine, 04330, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Christiana Care - Union Hospital

Elkton, Maryland, 21921, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Bronson Battle Creek

Battle Creek, Michigan, 49017, United States

Location

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, 49307, United States

Location

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, 49503, United States

Location

Mercy Health Saint Mary's

Grand Rapids, Michigan, 49503, United States

Location

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, 49503, United States

Location

Mercy Health Mercy Campus

Muskegon, Michigan, 49444, United States

Location

Spectrum Health Reed City Hospital

Reed City, Michigan, 49677, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

University of Missouri - Ellis Fischel

Columbia, Missouri, 65212, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Northwell Health NCORP

Lake Success, New York, 11042, United States

Location

Northwell Health/Center for Advanced Medicine

Lake Success, New York, 11042, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Wayne Memorial Hospital

Goldsboro, North Carolina, 27534, United States

Location

Vidant Oncology-Kinston

Kinston, North Carolina, 28501, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Cancer Care Associates-Norman

Norman, Oklahoma, 73071, United States

Location

Mercy Hospital Oklahoma City

Oklahoma City, Oklahoma, 73120, United States

Location

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Roper Hospital

Charleston, South Carolina, 29401, United States

Location

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, 05602, United States

Location

University of Vermont and State Agricultural College

Burlington, Vermont, 05405, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (5)

• Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.

  PMID: 36184192 DERIVED

• Mims AS, Kohlschmidt J, Borate U, Blachly JS, Orwick S, Eisfeld AK, Papaioannou D, Nicolet D, Mromicronzek K, Stein E, Bhatnagar B, Stone RM, Kolitz JE, Wang ES, Powell BL, Burd A, Levine RL, Druker BJ, Bloomfield CD, Byrd JC. A precision medicine classification for treatment of acute myeloid leukemia in older patients. J Hematol Oncol. 2021 Jun 23;14(1):96. doi: 10.1186/s13045-021-01110-5.

  PMID: 34162404 DERIVED

• Klepin HD, Ritchie E, Major-Elechi B, Le-Rademacher J, Seisler D, Storrick L, Sanford BL, Marcucci G, Zhao W, Geyer SA, Ballman KV, Powell BL, Baer MR, Stock W, Cohen HJ, Stone RM, Larson RA, Uy GL. Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: Report of CALGB 361006 (Alliance). J Geriatr Oncol. 2020 Jan;11(1):107-113. doi: 10.1016/j.jgo.2019.10.002. Epub 2019 Oct 24.

  PMID: 31668825 DERIVED

• Yin J, LaPlant B, Uy GL, Marcucci G, Blum W, Larson RA, Stone RM, Mandrekar SJ. Evaluation of event-free survival as a robust end point in untreated acute myeloid leukemia (Alliance A151614). Blood Adv. 2019 Jun 11;3(11):1714-1721. doi: 10.1182/bloodadvances.2018026112.

  PMID: 31171508 DERIVED

• Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, Klepin HD, Baer MR, Powell BL, Westervelt P, DeAngelo DJ, Stock W, Sanford B, Blum WG, Bloomfield CD, Stone RM, Larson RA. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017 Jan 24;1(5):331-340. doi: 10.1182/bloodadvances.2016003053.

  PMID: 29034366 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute

Interventions

Biopsy; Cytarabine; Daunorubicin; Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: Geoffrey Uy, MD
• Organization: Washington University School of Medicine

guy@dom.wustl.edu

Study Officials

• Geoffrey L Uy

  Alliance for Clinical Trials in Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2010
• First Posted: December 3, 2010
• Study Start: April 1, 2011
• Primary Completion: October 31, 2014
• Study Completion: April 15, 2021
• Last Updated: August 4, 2022
• Results First Posted: February 11, 2016

Record last verified: 2022-08

Locations

US (43)