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

Therapy-Related Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01253070
• Other study ID #: NCI-2011-02618
• Secondary ID: NCI-2011-02618CD
• Status: Completed
• Phase: Phase 2
• Start date: April 1, 2011
• Est. completion date: April 15, 2021

Study information

• Verified date: August 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: April 15, 2021
• Est. primary completion date: October 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• 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
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Promyelocytic, Acute
• Therapy-Related Acute Myeloid Leukemia

Intervention

Procedure:
• Biopsy
Undergo biopsy
• Bone Marrow Aspiration
Undergo bone marrow aspirate

Drug:
• Cytarabine
Given IV
• Daunorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Drug:
• Sorafenib Tosylate
Given PO

Locations

Country	Name	City	State
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Roper Hospital	Charleston	South Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Northwell Health NCORP	Lake Success	New York
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	North Shore University Hospital	Manhasset	New York
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Cancer Care Associates-Norman	Norman	Oklahoma
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	AdventHealth Orlando	Orlando	Florida
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Munson Medical Center	Traverse City	Michigan
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Time from registration to death (up to 10 years)
Secondary	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.	Time from registration to death or relapse (up to 10 years)