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A Phase II Study Incorporating Sorafenib (IND 69896, NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia


Phase 2
60 Years
N/A
Open (Enrolling)
Both
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

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Trial Information

A Phase II Study Incorporating Sorafenib (IND 69896, NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia


PRIMARY OBJECTIVES:

I. To determine if the 1-year overall survival rate of patients age >= 60 with internal
tandem duplications of fms-like tyrosine kinase (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.

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: This is a multicenter study.

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
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 twice daily 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 twice daily 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 twice daily 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
transplantation (HSCT) are encouraged to enroll in 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.

Patients may undergo bone marrow aspirate, tumor biopsy, and/or blood sampling at baseline
and periodically during study for cytogenetic, biomarker, and mutation analysis.

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 at least 10 years.


Inclusion Criteria:



- Unequivocal histologic diagnosis of AML according to World Health Organization (WHO)
criteria, EXCLUDING:

- Acute promyelocytic leukemia t(15;17)(q22;q12); PML-RARA

- Acute myeloid leukemia with t(8;21)(q22;q22); 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); CBFBMYH11
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)

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall survival (OS) rate

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Geoffrey Uy

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02618

NCT ID:

NCT01253070

Start Date:

April 2011

Completion Date:

Related Keywords:

  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Secondary Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Washington University School of MedicineSaint Louis, Missouri  63110
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
Eastern Maine Medical CenterBangor, Maine  04401
Weill Medical College of Cornell UniversityNew York, New York  10021
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Munson Medical CenterTraverse City, Michigan  49684
Brigham and Women's HospitalBoston, Massachusetts  02115
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Beebe Medical CenterLewes, Delaware  19958
Mecosta County Medical CenterBig Rapids, Michigan  49307
Mountainview MedicalBerlin, Vermont  05602
Harold Alfond Center for Cancer CareAugusta, Maine  04330
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
University Of VermontBurlington,, Vermont  05403
Virginia Commonwealth UniversityRichmond, Virginia  
Florida HospitalOrlando, Florida  32803
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Cooper Hospital University Medical CenterCamden, New Jersey  08103
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Kinston Medical Specialists PAKinston, North Carolina  28501
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
University of Missouri - Ellis FischelColumbia, Missouri  65203
Monter Cancer CenterLake Success, New York  11042
Spectrum Health Reed City HospitalReed City, Michigan  49677
Cancer Care Associates-MercyOklahoma City, Oklahoma  73120
Cancer and Leukemia Group BChicago, Illinois  60606
North Shore-LIJ Health System CCOPManhasset, New York  11030
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Bronson Battle CreekBattle Creek, Michigan  49017
Cancer Care Associates-NormanNorman, Oklahoma  73071