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

Myelogenous Leukemia Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00519090
• Other study ID #: CAMN107A2302
• Status: Terminated
• Phase: Phase 3
• First received: August 17, 2007
• Last updated: November 4, 2011
• Start date: October 2007
• Est. completion date: October 2008

Study information

• Verified date: November 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myelogenous Leukemia

Intervention

Drug:
• Imatinib
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.
• Nilotinib (AMN107)
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.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Darlinghurst
Australia	Novartis Investigative Site	Herston
Australia	Novartis Investigative Site	Liverpool
Australia	Novartis Investigative Site	Perth
Australia	Novartis Investigative Site	Prahran
Australia	Novartis Investigative Site	South Brisbane
Australia	Novartis Investigative Site	St. Leonards
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Brazil	Novartis Investigative Site	Mannheim
Brazil	Novartis Investigative Site	Porto Alegre
Brazil	Novartis Investigative Site	Sao Paulo
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Praha
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Eisensach
Germany	Novartis Investigative Site	Firenze
Germany	Novartis Investigative Site	Griefswald
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Leipzeg
Germany	Novartis Investigative Site	Postsdam
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Weiden
Italy	Novartis Investigative Site	Bologna
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Orbassano
Italy	Novartis Investigative Site	Reggio Calabra
Italy	Novartis Investigative Site	Roma
Japan	Novartis Investigative Site	Nagoya
Japan	Novartis Investigative Site	Oaska
Japan	Novartis Investigative Site	Tokyo
Korea, Republic of	Novartis Investigative Site	Hwasun-Gun
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca
Spain	Novartis Investigative Site	Santiago de Compostela
Spain	Novartis Investigative Site	Valencia
United States	Southern California Permanente Medical Group	Anaheim	California
United States	University of Michigan	Ann Arbor	Michigan
United States	Southern California Permanente Medical Group	Baldwin Park	California
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Indiana Blood and Marrow Transplantation	Beech Grove	Indiana
United States	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Duke University Hospital	Durham	North Carolina
United States	Southern California Permanente Medical Group	Fontana	California
United States	Jones Cancer Center	Germantown	Tennessee
United States	Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Kaiser Permanente Medical Group/Hayward Medical Center	Hayward	California
United States	University of Texas/MD Anderson Cancer Center	Houston	Texas
United States	Holden Cancer Center	Iowa City	Iowa
United States	Southern California Permanente Medical Group	Los Angeles	California
United States	Vanderbilt University	Nashville	Tennessee
United States	Kaiser Permanente Medical Group/Oakland Medical Center	Oakland	California
United States	Methodist Cancer Center	Omaha	Nebraska
United States	Southern California Permanente Medical Group	Panorama City	California
United States	Oregon Health Sciences University	Portland	Oregon
United States	Southern California Permanente Medical Group	Riverside	California
United States	Kaiser Permanente Medical Group/South San Francisco Medical Center	S. San Francisco	California
United States	Kaiser Permanente Medical Group/Sacramento Medical Center	Sacramento	California
United States	Southern California Permanente Medical Group	San Diego	California
United States	Kaiser Permanente Medical Group	San Francisco	California
United States	Kaiser Permanente Medical Group	San Jose	California
United States	Kaiser Permanente Medical Group/Santa Clara Medical Office	Santa Clara	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Arizona Cancer Center	Tucson	Arizona
United States	Kaiser Permanente Medical Group/Vallejo Medical Center	Vallejo	California
United States	Kaiser Permanente Medical Group/Walnut Creek Medical Center	Walnut Creek	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Southen California Permanente Medical Group	Woodland Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Czech Republic,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months	No
Secondary	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.	24 months	No

External Links

•   Chronic Myeloid Leukemia