Clinical trial NCT00079482: Study of CEP-701 (Lestaurtinib) in Patients With Acute Myeloid Leukemia (AML)
Official title: A Randomized, Open-Label Study of Oral CEP-701 Administered in Sequence With Standard Chemotherapy to Patients With Relapsed Acute Myeloid Leukemia (AML) Expressing FLT-3 Activating Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2004-03-10
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine whether CEP-701 given in sequence with induction chemotherapy increases the proportion of patients with relapsed acute myeloid leukemia (AML) who achieve a second complete remission (CR).

Detailed description: Patients randomly assigned to chemotherapy alone received the second course of induction chemotherapy as soon as clinically indicated; patients randomly assigned to receive chemotherapy plus sequential lestaurtinib had lestaurtinib withheld for 3 days (72 hours) before the start of the second 5-day course of chemotherapy and resumed lestaurtinib treatment 2 days (48 hours) after the final administration of the second course of chemotherapy.

Eligibility criteria: Inclusion criteria:

* cytological confirmation of AML;
* relapsed disease following first CR of 1 month(30days)to 24 months(730days). The time from first relapse to study entry (start of first course of induction chemotherapy) must be no longer than 30days;
* confirmation of FLT-3 activating mutation positive status after point of initial relapse;
* aged 18 years or older;
* written informed consent;
* ability to understand and comply with study restrictions;
* no comorbid conditions that would limit life expectancy to less than 3 months;
* ECOG Performance Score of 0, 1,or 2;
* women must be neither pregnant nor lactating, and either of non-childbearing potential or using adequate contraception with a negative pregnancy test at study entry

Exclusion criteria:

* bilirubin \> 2x ULN;
* ALT/AST \> 3x ULN;
* serum creatinine \> 1.5 mg/dL;
* resting ejection fraction of left ventricle l \< 45%(applies only to patients scheduled to receive mitoxantrone, etoposide, and cytarabine \[MEC\];
* untreated or progressive infection;
* any physical or psychiatric cdtn that may compromise participation in the study;
* known CNS involvement with AML;
* any previous treatment with a FLT-3 inhibitor;
* requires current treatment for HIV with protease inhibitors;
* active GI ulceration or bleeding;
* use of an investigational drug that is not expected to be cleared by the start of CEP-701 treatment

Primary outcomes:
measure: Determine whether CEP-701 given in sequence with induction chemotherapy increases the proportion of patients with relapsed AML who achieve a second complete remission or a complete remission with incomplete platelet count recovery.
timeFrame: 113 days
Secondary outcomes:
measure: - overall survival - event-free survival - remission duration - safety and tolerability of CEP-701 - pharmacokinetics of CEP-701 - CEP-701 inhibitory activity
timeFrame: 113 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Mayo-Scottsdale
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Medical Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Macon
country: United States
facility: ACORN-Central Georgia Hematology/Oncology
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Cancer Care Services
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Cancer Pavillion
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Shreveport
country: United States
facility: LSU Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Univeristy of Maryland Medicine - Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Tufts New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: The Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York Presbyterian
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: ACORN-The West Clinic
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Sydney
country: Australia
facility: Call For Information
state: New South Wales
city: Herston
country: Australia
facility: Call for Information
state: Queensland
city: South Brisbane
country: Australia
facility: Call For Information
state: Queensland
city: Adelaide
country: Australia
facility: Call For Information
state: South Australia
city: Fitzroy
country: Australia
facility: Call For Information
state: Victoria
city: Melbourne
country: Australia
facility: Call For Information
state: Victoria
city: Perth
country: Australia
facility: Call For Information
state: Western Australia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Quebec
country: Canada
facility: CHA Hospital Enfant-Jesus
city: Chemnitz
country: Germany
facility: Call For Information
city: Dresden
country: Germany
facility: Call For Information
city: Frankfurt
country: Germany
facility: Call For Information
city: Heidelberg
country: Germany
facility: Call For Information
city: Munster
country: Germany
facility: Call For Information
city: Stuttgart
country: Germany
facility: Call For Information
city: Haifa
country: Israel
facility: Call For Information
city: Petah-Tiqwa
country: Israel
facility: Call For Information
city: Tel Hashomer
country: Israel
facility: Call For Information
city: Bologna
country: Italy
facility: Call For Information
city: Roma
country: Italy
facility: Call For Information
city: Roma
country: Italy
facility: Call For Information
city: Turin
country: Italy
facility: Call For Information
city: Auckland
country: New Zealand
facility: Call For Information
city: Bialystok
country: Poland
facility: Call For Information
city: Gdansk
country: Poland
facility: Call For Information
city: Katowice
country: Poland
facility: Call For Information
city: Krakow
country: Poland
facility: Call For Information
city: Lodz
country: Poland
facility: Call For Information
city: Lublin
country: Poland
facility: Call For Information
city: Poznan
country: Poland
facility: Call For Information
city: Warszawa
country: Poland
facility: Call For Information
city: Warszawa
country: Poland
facility: Call For Information
city: Wroclaw
country: Poland
facility: Call For Information
city: Bucharest
country: Romania
facility: Call For Information
city: Iasi
country: Romania
facility: Call For Information
city: Moscow
country: Russian Federation
facility: Call For Information
city: Novosibirsk
country: Russian Federation
facility: Call For Information
city: St. Petersburg
country: Russian Federation
facility: Call For Information
city: St. Petersburg
country: Russian Federation
facility: Call For Information
city: Barcelona
country: Spain
facility: Call For Information
city: Valencia
country: Spain
facility: Call For Information
city: Lund
country: Sweden
facility: Call For Information
city: Stockholm
country: Sweden
facility: Call For Information
city: Cherkassy
country: Ukraine
facility: Call For Information
city: Kiev
country: Ukraine
facility: Call For Information
city: Kiev
country: Ukraine
facility: Call For Information
city: Lvov
country: Ukraine
facility: Call For Information
Study officials:
References:
citation: Levis M, Ravandi F, Wang ES, Baer MR, Perl A, Coutre S, Erba H, Stuart RK, Baccarani M, Cripe LD, Tallman MS, Meloni G, Godley LA, Langston AA, Amadori S, Lewis ID, Nagler A, Stone R, Yee K, Advani A, Douer D, Wiktor-Jedrzejczak W, Juliusson G, Litzow MR, Petersdorf S, Sanz M, Kantarjian HM, Sato T, Tremmel L, Bensen-Kennedy DM, Small D, Smith BD. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood. 2011 Mar 24;117(12):3294-301. doi: 10.1182/blood-2010-08-301796. Epub 2011 Jan 26.