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Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (ENEST)

Primary Purpose

Myelogenous Leukemia

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Imatinib
Nilotinib (AMN107)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelogenous Leukemia focused on measuring leukemia, bone marrow, leukemia symptoms, cml, complete blood count, lymphocyte, blood cancer, leukocytes, chronic leukemia, bone marrow biopsy, leukemia research, leukemia cells, bone marrow disease, chronic myeloid leukemia, blood cancer symptoms, white blood cell diseases, chronic myelogenous leukemia, leukemia treatment, leukemia facts, leucemia, facts about leukemia, myelogenous leukemia, newly diagnosed CML, suboptimal response, Philadelphia chromosome positive (Ph+), chronic myelogenous leukemia in chronic phase (CML-CP)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Diagnosis of Philadelphia chromosome positive chronic myelogenous leukemia in the chronic phase.

Patients with suboptimal cytogenetic response to a dose of 400 mg imatinib (first line therapy) defined as:

  • 6 to < 12 months of treatment and -have 36 - 95% Ph+ metaphases, or
  • 12 to <18 months of treatment and have 1 - 35% Ph+ metaphases (Standard cytogenetics, no FISH [fluorescence in situ hybridization] analysis was allowed).

Exclusion criteria:

  • Patient who have received more than 18 months of imatinib therapy
  • Patients who have achieved partial or complete cytogenetic response and lost that response prior to entering the study.
  • Prior treatment with greater than 400 mg/day imatinib.
  • Uncontrolled or significant cardiovascular disease.
  • Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
  • Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
  • Currently taking certain medications that could affect the rhythm of your heart.

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Arizona Cancer Center
  • Southern California Permanente Medical Group
  • Southern California Permanente Medical Group
  • Southern California Permanente Medical Group
  • Kaiser Permanente Medical Group/Hayward Medical Center
  • Southern California Permanente Medical Group
  • Kaiser Permanente Medical Group/Oakland Medical Center
  • Southern California Permanente Medical Group
  • Southern California Permanente Medical Group
  • Kaiser Permanente Medical Group/South San Francisco Medical Center
  • Kaiser Permanente Medical Group/Sacramento Medical Center
  • Southern California Permanente Medical Group
  • Kaiser Permanente Medical Group
  • Kaiser Permanente Medical Group
  • Kaiser Permanente Medical Group/Santa Clara Medical Office
  • Kaiser Permanente Medical Group/Vallejo Medical Center
  • Kaiser Permanente Medical Group/Walnut Creek Medical Center
  • Southen California Permanente Medical Group
  • Rocky Mountain Cancer Center
  • Northwestern Memorial Hospital
  • The University of Chicago Medical Center
  • Indiana Blood and Marrow Transplantation
  • Holden Cancer Center
  • Johns Hopkins Hospital
  • University of Michigan
  • Hematology Centers of Western Michigan
  • Methodist Cancer Center
  • The Cancer Center at Hackensack University Medical Center
  • Duke University Hospital
  • Wake Forest University Health Sciences
  • Oregon Health Sciences University
  • St. Luke's Hospital and Health Network
  • Jones Cancer Center
  • Vanderbilt University
  • University of Texas/MD Anderson Cancer Center
  • Swedish Cancer Institute
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Nilotinib (AMN107)

Imatinib

Arm Description

Outcomes

Primary Outcome Measures

Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib
Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.

Secondary Outcome Measures

Durable Complete Cytogenetic Response Rate
Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.

Full Information

First Posted
August 17, 2007
Last Updated
November 4, 2011
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00519090
Brief Title
Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Acronym
ENEST
Official Title
A Phase III Randomized, Open- Label Multi-center Study of Nilotinib Versus Imatinib in Adult Patients With Ph+ Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Cytogenetic Response (CyR) on Imatinib
Study Type
Interventional

2. Study Status

Record Verification Date
November 2011
Overall Recruitment Status
Terminated
Why Stopped
This study was terminated due to limited enrollment.
Study Start Date
October 2007 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, the efficacy and safety of nilotinib 400 mg twice daily, will be compared with imatinib 400 mg twice daily in patients with a suboptimal response to imatinib for their Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).
Detailed Description
This trial was to evaluate the CCyR rate at 12 months of nilotinib therapy when compared to imatinib treatment in patients with suboptimal response to imatinib. The patients were stratified by prior duration of initial imatinib treatment, and were randomized to receive either 400 mg/twice daily of continuous nilotinib or imatinib treatment. The first stratum patients were treated with imatinib = 6 to < 12 months and having at least a minimal cytogenetic, but no partial cytogenetic response; and the second stratum patients were treated with imatinib = 12 months to < 18 months and having partial cytogenetic response (PCyR), but no CCyR.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelogenous Leukemia
Keywords
leukemia, bone marrow, leukemia symptoms, cml, complete blood count, lymphocyte, blood cancer, leukocytes, chronic leukemia, bone marrow biopsy, leukemia research, leukemia cells, bone marrow disease, chronic myeloid leukemia, blood cancer symptoms, white blood cell diseases, chronic myelogenous leukemia, leukemia treatment, leukemia facts, leucemia, facts about leukemia, myelogenous leukemia, newly diagnosed CML, suboptimal response, Philadelphia chromosome positive (Ph+), chronic myelogenous leukemia in chronic phase (CML-CP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nilotinib (AMN107)
Arm Type
Experimental
Arm Title
Imatinib
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Imatinib
Other Intervention Name(s)
STI571, imatinib mesylate, Glivec®, Gleevec®
Intervention Description
Administered orally as a single agent on a continuous daily schedule given 400 mg bid (twice daily) with food. One cycle comprised of 28 days.
Intervention Type
Drug
Intervention Name(s)
Nilotinib (AMN107)
Intervention Description
Administered orally as a single agent on a continuous daily schedule of 400 mg bid (2 x 200 mg twice daily) without food. Once cycle comprised of 28 days.
Primary Outcome Measure Information:
Title
Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib
Description
Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Durable Complete Cytogenetic Response Rate
Description
Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Diagnosis of Philadelphia chromosome positive chronic myelogenous leukemia in the chronic phase. Patients with suboptimal cytogenetic response to a dose of 400 mg imatinib (first line therapy) defined as: 6 to < 12 months of treatment and -have 36 - 95% Ph+ metaphases, or 12 to <18 months of treatment and have 1 - 35% Ph+ metaphases (Standard cytogenetics, no FISH [fluorescence in situ hybridization] analysis was allowed). Exclusion criteria: Patient who have received more than 18 months of imatinib therapy Patients who have achieved partial or complete cytogenetic response and lost that response prior to entering the study. Prior treatment with greater than 400 mg/day imatinib. Uncontrolled or significant cardiovascular disease. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon) Currently taking certain medications that could affect the rhythm of your heart. Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85701
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Baldwin Park
State/Province
California
ZIP/Postal Code
91706
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Fontana
State/Province
California
ZIP/Postal Code
92334
Country
United States
Facility Name
Kaiser Permanente Medical Group/Hayward Medical Center
City
Hayward
State/Province
California
ZIP/Postal Code
94540
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Los Angeles
State/Province
California
ZIP/Postal Code
90001
Country
United States
Facility Name
Kaiser Permanente Medical Group/Oakland Medical Center
City
Oakland
State/Province
California
ZIP/Postal Code
94601
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Panorama City
State/Province
California
ZIP/Postal Code
91402
Country
United States
Facility Name
Southern California Permanente Medical Group
City
Riverside
State/Province
California
ZIP/Postal Code
92501
Country
United States
Facility Name
Kaiser Permanente Medical Group/South San Francisco Medical Center
City
S. San Francisco
State/Province
California
ZIP/Postal Code
94101
Country
United States
Facility Name
Kaiser Permanente Medical Group/Sacramento Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
94203
Country
United States
Facility Name
Southern California Permanente Medical Group
City
San Diego
State/Province
California
ZIP/Postal Code
92101
Country
United States
Facility Name
Kaiser Permanente Medical Group
City
San Francisco
State/Province
California
ZIP/Postal Code
94101
Country
United States
Facility Name
Kaiser Permanente Medical Group
City
San Jose
State/Province
California
ZIP/Postal Code
95101
Country
United States
Facility Name
Kaiser Permanente Medical Group/Santa Clara Medical Office
City
Santa Clara
State/Province
California
ZIP/Postal Code
95050
Country
United States
Facility Name
Kaiser Permanente Medical Group/Vallejo Medical Center
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
Kaiser Permanente Medical Group/Walnut Creek Medical Center
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94595
Country
United States
Facility Name
Southen California Permanente Medical Group
City
Woodland Hills
State/Province
California
ZIP/Postal Code
91364
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80201
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60601
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60601
Country
United States
Facility Name
Indiana Blood and Marrow Transplantation
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
Holden Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52240
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48103
Country
United States
Facility Name
Hematology Centers of Western Michigan
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49501
Country
United States
Facility Name
Methodist Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68101
Country
United States
Facility Name
The Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Duke University Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27101
Country
United States
Facility Name
Oregon Health Sciences University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Facility Name
St. Luke's Hospital and Health Network
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Facility Name
Jones Cancer Center
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37201
Country
United States
Facility Name
University of Texas/MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77001
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Novartis Investigative Site
City
Darlinghurst
Country
Australia
Facility Name
Novartis Investigative Site
City
Herston
Country
Australia
Facility Name
Novartis Investigative Site
City
Liverpool
Country
Australia
Facility Name
Novartis Investigative Site
City
Perth
Country
Australia
Facility Name
Novartis Investigative Site
City
Prahran
Country
Australia
Facility Name
Novartis Investigative Site
City
South Brisbane
Country
Australia
Facility Name
Novartis Investigative Site
City
St. Leonards
Country
Australia
Facility Name
Novartis Investigative Site
City
Brugge
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
Country
Belgium
Facility Name
Novartis Investigative Site
City
Mannheim
Country
Brazil
Facility Name
Novartis Investigative Site
City
Porto Alegre
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
Country
Brazil
Facility Name
Novartis Investigative Site
City
Olomouc
Country
Czech Republic
Facility Name
Novartis Investigative Site
City
Praha
Country
Czech Republic
Facility Name
Novartis Investigative Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigative Site
City
Duesseldorf
Country
Germany
Facility Name
Novartis Investigative Site
City
Eisensach
Country
Germany
Facility Name
Novartis Investigative Site
City
Firenze
Country
Germany
Facility Name
Novartis Investigative Site
City
Griefswald
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
Country
Germany
Facility Name
Novartis Investigative Site
City
Jena
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzeg
Country
Germany
Facility Name
Novartis Investigative Site
City
Postsdam
Country
Germany
Facility Name
Novartis Investigative Site
City
Rostock
Country
Germany
Facility Name
Novartis Investigative Site
City
Stuttgart
Country
Germany
Facility Name
Novartis Investigative Site
City
Weiden
Country
Germany
Facility Name
Novartis Investigative Site
City
Bologna
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
Country
Italy
Facility Name
Novartis Investigative Site
City
Orbassano
Country
Italy
Facility Name
Novartis Investigative Site
City
Reggio Calabra
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
Country
Italy
Facility Name
Novartis Investigative Site
City
Nagoya
Country
Japan
Facility Name
Novartis Investigative Site
City
Oaska
Country
Japan
Facility Name
Novartis Investigative Site
City
Tokyo
Country
Japan
Facility Name
Novartis Investigative Site
City
Hwasun-Gun
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Barcelona
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
Country
Spain
Facility Name
Novartis Investigative Site
City
Salamanca
Country
Spain
Facility Name
Novartis Investigative Site
City
Santiago de Compostela
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
24472814
Citation
Agrawal M, Hanfstein B, Erben P, Wolf D, Ernst T, Fabarius A, Saussele S, Purkayastha D, Woodman RC, Hofmann WK, Hehlmann R, Hochhaus A, Muller MC. MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure. Leukemia. 2014 Jul;28(7):1478-85. doi: 10.1038/leu.2014.6. Epub 2014 Jan 10.
Results Reference
derived

Learn more about this trial

Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

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