Study of CEP-701 (Lestaurtinib) in Patients With Acute Myeloid Leukemia (AML)

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

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).

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: CEP-701; Drug: Mitozantrone, Etoposide, Cytarabine (combination Chemotherapy); Drug: high-dose cytarabine

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.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2065
      • Call For Information
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Call For Information
    • South Brisbane, Queensland, Australia, 4101
      • Call For Information
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Call For Information
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Call For Information
    • Melbourne, Victoria, Australia, 3004
      • Call For Information
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Call For Information
• Canada
  • Quebec, Canada, G1J1Z4
    • CHA Hospital Enfant-Jesus
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Hospital
• Germany
  • Chemnitz, Germany, 09113
    • Call For Information
  • Dresden, Germany, 01307
    • Call For Information
  • Frankfurt, Germany, 60590
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  • Heidelberg, Germany, 69120
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  • Munster, Germany, 48129
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  • Stuttgart, Germany, 70376
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• Israel
  • Haifa, Israel, 31096
    • Call For Information
  • Petah-Tiqwa, Israel, 49100
    • Call For Information
  • Tel Hashomer, Israel, 52621
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• Italy
  • Bologna, Italy, 41038
    • Call For Information
  • Roma, Italy, 00133
    • Call For Information
  • Roma, Italy, 00161
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  • Turin, Italy, 10043
    • Call For Information
• New Zealand
  • Auckland, New Zealand, 1023
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• Poland
  • Bialystok, Poland, 15276
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  • Gdansk, Poland, 80952
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  • Katowice, Poland, 40032
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  • Krakow, Poland, 31501
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  • Lodz, Poland, 93510
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  • Lublin, Poland, 20022
    • Call For Information
  • Poznan, Poland, 60569
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  • Warszawa, Poland, 02097
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  • Warszawa, Poland, 02776
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  • Wroclaw, Poland, 50369
    • Call For Information
• Romania
  • Bucharest, Romania, 030171
    • Call For Information
  • Iasi, Romania, 700111
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• Russian Federation
  • Moscow, Russian Federation, 125167
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  • Novosibirsk, Russian Federation, 630099
    • Call For Information
  • St. Petersburg, Russian Federation, 197022
    • Call For Information
  • St. Petersburg, Russian Federation, 197110
    • Call For Information
• Spain
  • Barcelona, Spain, 08041
    • Call For Information
  • Valencia, Spain, 46009
    • Call For Information
• Sweden
  • Lund, Sweden, SE-22185
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  • Stockholm, Sweden, SE-17176
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• Ukraine
  • Cherkassy, Ukraine, 18009
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  • Kiev, Ukraine, 03115
    • Call For Information
  • Kiev, Ukraine, 04112
    • Call For Information
  • Lvov, Ukraine, 79044
    • Call For Information
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo-Scottsdale
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90033
      • USC/Norris Cancer Center
    • Stanford, California, United States, 94305
      • Stanford Medical Center
  • Florida
    • Tampa, Florida, United States, 33606
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Macon, Georgia, United States, 31201
      • ACORN-Central Georgia Hematology/Oncology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Cancer Care Services
    • Indianapolis, Indiana, United States, 46202
      • Indiana Cancer Pavillion
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins
    • Baltimore, Maryland, United States, 21201
      • Univeristy of Maryland Medicine - Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts New England Medical Center
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • The Mayo Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • New York Presbyterian
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • ACORN-The West Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Induction chemotherapy with or without sequential treatment with oral CEP-701 at 80 mg bid. For patients with duration of first CR of 1 to 6 months, the induction regimen will be MEC.	Drug: CEP-701; Other Names: lestaurtinib; Drug: Mitozantrone, Etoposide, Cytarabine (combination Chemotherapy); Chemotherapy; Other Names: MEC
Active Comparator: 2; Induction chemotherapy with or without sequential treatment with oral CEP-701 at 80 mg bid. For patients with duration of first CR of more than 6 months to 24 months, the induction regimen will be HiDAC.	Drug: CEP-701; Other Names: lestaurtinib; Drug: high-dose cytarabine; Chemotherapy; Other Names: HiDAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	113 days

Secondary Outcome Measures

Outcome Measure	Time Frame
- overall survival - event-free survival - remission duration - safety and tolerability of CEP-701 - pharmacokinetics of CEP-701 - CEP-701 inhibitory activity	113 days

Collaborators and Investigators

• Sponsor: Cephalon

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 9, 2004
• First Posted (Estimate): March 10, 2004

Study Record Updates

• Last Update Posted (Estimate): July 21, 2016
• Last Update Submitted That Met QC Criteria: July 19, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Cytarabine; Mitoxantrone
• Other Study ID Numbers: C701a/204/ON/US