Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia Clinical Trial

Official title:

A Phase III Study of STI571 Versus Interferon-α (IFN-α) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00333840
• Other study ID #: CSTI571A 0106
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2006
• Last updated: August 7, 2013
• Start date: June 2000
• Est. completion date: March 2012

Study information

• Verified date: August 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines AgencyAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate and compare the side effects and anti-leukemic benefits of imatinib with those of interferon and Ara-C for patients who have chronic myeloid leukemia (CML) in the chronic phase. Patients in this study will be randomized (1:1) to receive either interferon plus Ara-C or imatinib as initial treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1106
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria:

• Must have signed consent for Amendment 5

• Must have completed visit 62 of the core IRIS trial or be in follow-up

• Must be on STI571 treatment

• If on IFN treatment, must be willing to cross over to STI571 treatment

Exclusion criteria:

• Patients who have discontinued from the study and are in follow-up

• Patients who are on IFN treatment and do not want to cross over to STI571 treatment

• Patients who have not consented to amendment 5

• Patients who did not complete the amendment 5 protocol

Additional protocol-defined inclusion/exclusion criteria may apply

Study Design

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

Related Conditions & MeSH terms

• Abnormal Karyotype
• Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Philadelphia Chromosome

Intervention

Drug:
• imatinib mesilate
imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules.
• interferon-alpha (INF-a)
interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m^2/day.
• cytarabine (ARA-C)
cytarabine 20 mg/m^2/day (max 40 mg) SC for 10 days every month.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Adelaide
Australia	Novartis Investigative Site	Brisbane
Australia	Novartis Investigative Site	Darlinghurst
Australia	Novartis Investigative Site	East Melbourne
Australia	Novartis Investigative Site	Nedlands
Australia	Novartis Investigative Site	Parkville
Australia	Novartis Investigative Site	Prahan
Australia	Novartis Investigative Site	South Brisbane
Australia	Novartis Investigative Site	St. Leonards
Australia	Novartis Investigative Site	Sydney
Australia	Novartis Investigative Site	Westmead
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Godinne
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Denmark	Novartis Investigative Site	Arhus
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Herlev
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pessac
France	Novartis Investigative Site	Poitiers
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Vandoeuvre-les-Nancy
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dusseldorf
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Munchen
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Stuttgart
Italy	Novartis Investigative Site	Bari
Italy	Novartis Investigative Site	Bologna
Italy	Novartis Investigative Site	Firenze
Italy	Novartis Investigative Site	Genova
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Orbassano
Italy	Novartis Investigative Site	Pavia
Italy	Novartis Investigative Site	Pescara
Italy	Novartis Investigative Site	Pisa
Italy	Novartis Investigative Site	Reggio Calabria
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Rotterdam
New Zealand	Novartis Investigative Site	Auckland
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Tromso
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca
Spain	Novartis Investigative Site	Valencia
Sweden	Novartis Investigative Site	Goteborg
Sweden	Novartis Investigative Site	Linkoping
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Orebro
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Umea
Sweden	Novartis Investigative Site	Uppsala
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	St. Gallen
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Cambridge
United Kingdom	Novartis Investigative Site	Cardiff
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Plymouth
United States	Novartis Investigative Site	Alburquerque	New Mexico
United States	Novartis Investigative Site	Alburquerque	New Mexico
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Beech Grove	Indiana
United States	Novartis Investigative Site	Berkeley	California
United States	Novartis Investigative Site	Billings	Montana
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Campbell	California
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Decatur	Illinois
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Duarte	California
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	East Lansing	Michigan
United States	Novartis Investigative Site	Farmington	New Mexico
United States	Novartis Investigative Site	Hackensack	New Jersey
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	La Jolla	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Memphis	Tennessee
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Montgomery	Alabama
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Pittsburg	Pennsylvania
United States	Novartis Investigative Site	Pittsburg	Pennsylvania
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Providence	Rhode Island
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Syracuse	New York
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Winston-Salem	North Carolina
United States	Novartis Investigative Site	Witchita	Kansas
United States	Novartis Investigative Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Netherlands,  New Zealand,  Norway,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)	Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.	12,24,36,48,60,72,84,96,108,120,132 and 144 months	No
Secondary	Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)	Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment: progression to Accelerated Phase (AP) or Blast Crisis (BC); loss of Complete Hematological Response (CHR); loss of Major Cytogenetic Response (MCyR) confirmed; loss of Major Cytogenetic Response (MCyR) unconfirmed; increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC); death (due to any cause when reported as primary reason for discontinuation of treatment).; Kaplan Meier estimates of the percentage of participants with Event Free Survival at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.	12,24,36,48,60,72,84,96,108,120,132 and 144 months	No
Secondary	Percentage of Participants With Event Free Survival Events (All Randomized Participants)	Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment: progression to Accelerated Phase (AP) or Blast Crisis (BC); loss of Complete Hematological Response (CHR); loss of Major Cytogenic Response (MCyR) confirmed; loss of Major Cytogenic Response (MCyR) unconfirmed; increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC); death (due to any cause when reported as primary reason for discontinuation of treatment).; The percentage of participants with Event Free Survival events in each category was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.	144 months	No
Secondary	Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)	Time to progression to AP/BC is defined as the time between randomization and either of the following events on treatment: death (due to CML when reported as primary reason for discontinuation of treatment) or progression to Accelerated Phase or Blast Crisis and is censored at last examination date for patients without event. No data after discontinuation of study treatment was included. The Kaplan Meier estimates of the percentage of participants with survival without progression to AP/BC at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.	12,24,36,48,60,72,84,96,108,120,132 and 144 months	No
Secondary	Percentage of Participants With Best Cytogenetic Response (First-line Treatment)	Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Philadelphia chromosome positive (Ph+) metaphases) and amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.; Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and = 35 % of Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated.	144 months	No
Secondary	Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)	Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Ph chromosome (Ph+) containing metaphases) and the amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.; Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and = 35 % Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated.	144 months	No
Secondary	Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)	A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant	144 months	Yes
Secondary	Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)	A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant	144 months	Yes
Secondary	Percentage of Participants With Major Molecular Response (First-line Treatment)	Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of = 0.1% according to the international scale.	12,24,36,48,60,72,84,96,108,120,132 and 144 months	No
Secondary	Percentage of Participants With Major Molecular Response (Second-line Treatment)	Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of = 0.1% according to the international scale.	12,24,36,48,60,72,84,96,108,120,132 and 144 months	No