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

NCT ID: NCT01253070

Last Updated: 2022-08-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-01

Study Completion Date

2021-04-15

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspirate

Cytarabine

Intervention Type DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Sorafenib Tosylate

Intervention Type DRUG

Given PO

Interventions

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Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspirate

Intervention Type PROCEDURE

Cytarabine

Given IV

Intervention Type DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Sorafenib Tosylate

Given PO

Intervention Type DRUG

Other Intervention Names

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BIOPSY_TYPE Bx .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 Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem Quality of Life Assessment BAY 43-9006 Tosylate BAY 54-9085 Nexavar sorafenib

Eligibility Criteria

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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 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)
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey L Uy

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Beebe Medical Center

Lewes, Delaware, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Christiana Care - Union Hospital

Elkton, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Bronson Battle Creek

Battle Creek, Michigan, United States

Site Status

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, United States

Site Status

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Site Status

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Site Status

Spectrum Health Reed City Hospital

Reed City, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Site Status

Northwell Health NCORP

Lake Success, New York, United States

Site Status

Northwell Health/Center for Advanced Medicine

Lake Success, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Site Status

Vidant Oncology-Kinston

Kinston, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Cancer Care Associates-Norman

Norman, Oklahoma, United States

Site Status

Mercy Hospital Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Roper Hospital

Charleston, South Carolina, United States

Site Status

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

Site Status

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 36184192 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34162404 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31668825 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31171508 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29034366 (View on PubMed)

Other Identifiers

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NCI-2011-02618

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000689593

Identifier Type: -

Identifier Source: secondary_id

CALGB-11001

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-11001

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02618

Identifier Type: -

Identifier Source: org_study_id

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