Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This phase II clinical trial is studying the side effects and how well giving sorafenib tosylate together with chemotherapy works 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 together with combination chemotherapy may kill more cancer cells.

Further Study Information

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.

Eligibility Criteria

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)

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Geoffrey Uy

Principal Investigator

U.S.A.
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Stephen Scott Grubbs	Ph: 302-733-6227
	Newark
	Helen F. Graham Cancer Center at Christiana Hospital
		Stephen Scott Grubbs	Ph: 302-733-6227
Florida
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Lee M. Zehngebot	Ph: 407-303-5623
Illinois
	Chicago
	Cancer and Leukemia Group B
		Geoffrey L Uy	Ph: 800-600-3606
	University of Chicago Cancer Research Center
		Wendy Stock	Ph: 773-834-7424
	Evanston
	CCOP - Evanston
		Lynne S. Kaminer	Ph: 847-570-1381
Indiana
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Rao Nattam	Ph: 260-484-8830
			Email: ledgar@fwmoh.com
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Katarzyna Jamieson	Ph: 877-668-0683
Maine
	Augusta
	Harold Alfond Center for Cancer Care
		Thomas Henry Openshaw	Ph: 207-973-4274
	Bangor
	CancerCare of Maine at Eastern Maine Medical Center
		Thomas Henry Openshaw	Ph: 207-973-4274
Maryland
	Baltimore
	Greenebaum Cancer Center at University of Maryland Medical Center
		Maria R. Baer	Ph: 800-888-8823
	Elkton MD
	Union Hospital of Cecil County
		Stephen Scott Grubbs	Ph: 302-733-6227
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
		Richard Maury Stone	Ph: 866-790-4500
	Massachusetts General Hospital
		Richard Maury Stone	Ph: 866-790-4500
Michigan
	Battle Creek
	Battle Creek Health System Cancer Care Center
		Gilbert D Padula	Ph: 616-685-5225
	Big Rapids
	Mecosta County Medical Center
		Gilbert D Padula	Ph: 616-685-5225
	Grand Rapids
	Butterworth Hospital at Spectrum Health
		Gilbert D Padula	Ph: 616-685-5225
	CCOP - Grand Rapids
		Gilbert D Padula	Ph: 616-685-5225
	Lacks Cancer Center at Saint Mary's Health Care
		Gilbert D Padula	Ph: 616-685-5225
	Muskegon
	Mercy General Health Partners
		Gilbert D Padula	Ph: 616-685-5225
	Reed City
	Spectrum Health Reed City Hospital
		Gilbert D Padula	Ph: 616-685-5225
	Traverse City
	Munson Medical Center
		Gilbert D Padula	Ph: 616-685-5225
Missouri
	Columbia
	Ellis Fischel Cancer Center at University of Missouri - Columbia
		Carl E. Freter	Ph: 573-882-7440
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Geoffrey L Uy	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
New Hampshire
	Lebanon
	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
		Christopher H Lowrey	Ph: 800-639-6918
			Email: cancer.research.nurse@dartmouth.edu
New Jersey
	Camden
	Cancer Institute of New Jersey at Cooper University Hospital - Camden
		Stephen Scott Grubbs	Ph: 302-733-6227
New York
	Lake Success
	Monter Cancer Center of the North Shore-LIJ Health System
		Jonathan Eliahu Kolitz	Ph: 516-562-3467
	Manhasset
	CCOP - North Shore University Hospital
		Jonathan Eliahu Kolitz	Ph: 516-562-3467
	Don Monti Comprehensive Cancer Center at North Shore University Hospital
		Jonathan Eliahu Kolitz	Ph: 516-562-3467
	New Hyde Park
	Long Island Jewish Medical Center
		Jonathan Eliahu Kolitz	Ph: 516-562-3467
	New York
	New York Weill Cornell Cancer Center at Cornell University
		Ellen K Ritchie	Ph: 212-746-1848
	Syracuse
	SUNY Upstate Medical University Hospital
		Teresa C. Gentile	Ph: 315-464-5476
North Carolina
	Goldsboro
	Wayne Memorial Hospital, Incorporated
		James N. Atkins	Ph: 919-580-0000
	Kinston
	Kinston Medical Specialists
		Peter R. Watson	Ph: 252-559-2200
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Bayard L. Powell	Ph: 336-713-6771
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
		Guido Marcucci	Ph: 866-627-7616
			Email: osu@emergingmed.com
Oklahoma
	Norman
	Cancer Care Associates - Norman
		Vikki Ann Canfield	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
	Oklahoma City
	Cancer Care Associates - Mercy Campus
		Vikki Ann Canfield	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Pennsylvania
	Pittsburgh
	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
		John Lister	Ph: 412-578-5000
Vermont
	Berlin
	Mountainview Medical
		Gurpreet Lamba	Ph: 718-818-2952
	Burlington
	Vermont Cancer Center at University of Vermont
		Gurpreet Lamba	Ph: 718-818-2952
Virginia
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Prithviraj Bose	Ph: 804-628-1939

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01253070
Information obtained from ClinicalTrials.gov on April 22, 2013