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Acute Myeloid Leukemia With FLT3/ITD MutationPhase 2NCT01253070

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

A Phase 2 study testing Biopsy, Bone Marrow Aspiration and Cytarabine in people with Acute Myeloid Leukemia With FLT3/ITD Mutation and Acute Myeloid Leukemia With Inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, run by National Cancer Institute (NCI) at 43 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Biopsy, Bone Marrow Aspiration and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
43 sitesUnited States
Study dates
1 Apr 2011to 15 Apr 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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)

Who cannot join

None listed.

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Spectrum Health Big Rapids Hospital

    Big Rapids, Michigan, 49307

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Roper Hospital

    Charleston, South Carolina, 29401

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Missouri - Ellis Fischel

    Columbia, Missouri, 65212

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Christiana Care - Union Hospital

    Elkton, Maryland, 21921

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Cancer Research Consortium of West Michigan NCORP

    Grand Rapids, Michigan, 49503

  • Mercy Health Saint Mary's

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Vidant Oncology-Kinston

    Kinston, North Carolina, 28501

  • Northwell Health NCORP

    Lake Success, New York, 11042

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Mercy Health Mercy Campus

    Muskegon, Michigan, 49444

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Cancer Care Associates-Norman

    Norman, Oklahoma, 73071

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • West Penn Hospital

    Pittsburgh, Pennsylvania, 15224

  • Spectrum Health Reed City Hospital

    Reed City, Michigan, 49677

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Biopsy, Bone Marrow Aspiration, Cytarabine, Daunorubicin Hydrochloride, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Myelomonocytic, Acute, Leukemia, Promyelocytic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspirate

  • CytarabineDrug

    Also called .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

    Given IV

  • Daunorubicin HydrochlorideDrug

    Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Sorafenib TosylateDrug

    Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

    Given PO

Study groups in NCT01253070
Study groupRoleWhat they receive
Treatment (daunorubicin, cytarabine, sorafenib tosylate)ExperimentalINDUCTION 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year

Secondary outcomes (2)

  1. OS

    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.

    Measured: Time from registration to death (up to 10 years)

  2. Event-free Survival

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2010 (estimated)
  2. Study start1 Apr 2011
  3. Primary completion31 Oct 2014
  4. Study completion15 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01253070
Sponsor's protocol ID
NCI-2011-02618
Other IDs
NCI-2011-02618, CDR0000689593, CALGB-11001, CALGB-11001, U10CA180821, U10CA031946
Status last verified
Aug 2022
First submitted
2 Dec 2010
Last updated
4 Aug 2022
Data monitoring committee
No

Publications

  • 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.

    PubMed 36184192

  • 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.

    PubMed 34162404

  • 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.

    PubMed 31668825

  • 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.

    PubMed 31171508

  • 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.

    PubMed 29034366

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Bone Marrow Aspiration and Cytarabine in people with Acute Myeloid Leukemia With FLT3/ITD Mutation and Acute Myeloid Leukemia With Inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, run by National Cancer Institute (NCI) at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) Rate (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01253070, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2022.

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