Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
- Conditions
- Chronic Myelogenous Leukemia
- Interventions
- Registration Number
- NCT00333840
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1106
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description imatinib (STI571) imatinib mesilate In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injection for 10 days every month. Maximum study duration was 11.5 years. imatinib (STI571) cytarabine (ARA-C) In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injection for 10 days every month. Maximum study duration was 11.5 years. IFN-a+Ara-C imatinib mesilate In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years. IFN-a+Ara-C cytarabine (ARA-C) In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years. imatinib (STI571) interferon-alpha (INF-a) In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injection for 10 days every month. Maximum study duration was 11.5 years. IFN-a+Ara-C interferon-alpha (INF-a) In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.
- Primary Outcome Measures
Name Time Method Kaplan-Meier Estimates of Overall Survival (All Randomized Participants) 12,24,36,48,60,72,84,96,108,120,132 and 144 months 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment) 144 months 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
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants) 12,24,36,48,60,72,84,96,108,120,132 and 144 months 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.Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants) 12,24,36,48,60,72,84,96,108,120,132 and 144 months 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.
Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment) 144 months 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
Percentage of Participants With Event Free Survival Events (All Randomized Participants) 144 months 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.Percentage of Participants With Major Molecular Response (Second-line Treatment) 12,24,36,48,60,72,84,96,108,120,132 and 144 months 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.
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment) 144 months 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.Percentage of Participants With Major Molecular Response (First-line Treatment) 12,24,36,48,60,72,84,96,108,120,132 and 144 months 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.
Percentage of Participants With Best Cytogenetic Response (First-line Treatment) 144 months 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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇬🇧Plymouth, United Kingdom