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Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity) (TOPS)

Primary Purpose

Leukemia, Myeloid, Chronic Phase

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

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Chronic Phase focused on measuring CML, Philadelphia positive, Bcr-abl, imatinib mesylate, Chronic myeloid leukemia (CML) in chronic phase

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis) Diagnosis of chronic myelogenous leukemia (CML) in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Breakpoint cluster region gene-abelson proto-oncogene (Bcr-Abl) Documented chronic phase CML Adequate end organ function as defined by: total bilirubin < 1.5 x Upper Limit of Normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x ULN creatinine < 1.5 x ULN Exclusion Criteria: Patients in late chronic phase, accelerated phase, or blastic phase are excluded Patients who have received other investigational agents Patients who received Gleevec/Glivec for any duration prior to study entry, with the exception of those patients successfully completing [CSTI571A2107 (NCT00428909)] study immediately prior to the participation in this study Patient received any treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes,chronic renal disease) Patient previously received radiotherapy to ≥ 25% of the bone marrow Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥ 3 Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment Other protocol-defined inclusion/exclusion criteria applied.

Sites / Locations

  • University of South Alabama
  • Alta Bates Comprehsenive Cancer Center
  • University of Miami
  • South Bay Oncology Hematology Partners
  • UCLA Medical Center
  • Rocky Mountain Cancer Center
  • Osler Medical Inc.
  • Advanced Medical Specialists
  • Integrated Community Oncology Network
  • Hematology-Oncology Associates, P.A.
  • Palm Beach Cancer Institute
  • Palm Beach Cancer Institute
  • Cancer Research Center of Hawaii
  • Rush University Medical Center
  • Indiana Blood and Marrow Institutw
  • Indiana Blood and Marrow Transplant
  • University of Iowa Hospitals & Clinic
  • University of Kentucky - C201 Clinic
  • University of Kentucky
  • Lousville Oncology, Clinical Research Program M-25
  • Jayne S. Gurtler, MD, Laura A. Brinz, MD & Angelo Russo, MD
  • Hematology and Oncology Specialists
  • LSU Health Science Center
  • LSU Health Scine Center
  • St. Agnes Hospital
  • Great Lakes Cancer Institute
  • U of Minnesota
  • University of Minnesota
  • Cancer Center at Hackensack University Medical Center
  • Hackensack University Medical Center
  • San Juan Oncology Associates
  • Roswell Park Cancer Institute
  • Duke University Medical Center
  • Cancer Center of the Carolinas
  • Wake Forest University Health Sciences
  • University Hospitals of Cleveland, Case Comprehensive Cancer Center
  • Cleveland Clinic Foundation
  • Kaiser Permanente Northwest Region Oncology/Hemacology
  • Kaiser Permanente Northwest Region
  • Western Pennsylvania Hospital
  • University of Pittsburg, Hillman Cancer Center
  • MUSC Hollings Cancer Center
  • Cancer Center of the Carolinas
  • Cancer Centers of the Carolinas
  • The Jones Clinic
  • Sarah Cannon Research Institute
  • UT Southwestern Harold C. Simmons Comprehensive Cancer Center
  • University of Texas / MD Anderson Cancer Center
  • MD Anderson Cancer Center
  • University of Virgina Cancer Center, UVA Division of Hematology & Oncology
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Imatinib 400 mg

imatinib 800 mg

Arm Description

Oral dose of 400mg Imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.

Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.

Outcomes

Primary Outcome Measures

Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).

Secondary Outcome Measures

Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
Cytogenetic response (CyR)is the percentage of Philadelphia chromosome positive metaphases (among at least 20 metaphase cells in bone marrow (BM)) with Complete Cytogenetic Response (CCyR) being 0 percent.
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
Complete Hematologic Response (CHR) is where all of the following criteria must be present for ≥4 weeks: White Blood Cell (WBC) count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) < 5% in PB and No evidence of extramedullary involvement.
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
"Undetectable levels" or Complete molecular response is defined as Bcr-Abl ratio (%) on international scale (IS) <= 0.0032% (≥ 4.5 log reduction of BCR-Abl transcripts from a standardized baseline).
Time to First Major Molecular Response
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally). Time to MMR (months) = (date of first MMR or censoring - date of randomization + 1) / 30.4375. Time to first MMR was evaluated using the Kaplan-Meier method
Time to First Complete Cytogenetic Response
Cytogenetic response (CyR) is the percentage of Philadelphia positive metaphases (among at least 20 metaphase cells in Bone Marrow) with Complete Cytogenetic Response (CCyR) being 0 percent. Time to CCyR (months) = (date of first CCyR or censoring - date of randomization + 1) / 30.4375. Time to first CCyR was evaluated using the Kaplan-Meier method.
Time to First Complete Hematological Response (CHR)]
Complete Hematological Response (CHR) is defined is where all of the following criteria must be present for ≥4 weeks: White Blood Cell (WBC) count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) < 5% in PB and No evidence of extramedullary involvement. Time to CHR (months) = (date of first CHR or censoring - date of randomization + 1) / 30.4375. Time to first CHR was evaluated using the Kaplan-Meier method.
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
EFS on treatment was defined as time between randomization and either (1) death due to any cause during study treatment, (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment, (3) loss of complete hematological response (CHR), or (4) loss of major cytogenic response (MCyR) while on treatment. Estimated rate of EFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
PFS on study which was defined as time between randomization and either (1) death due to any cause on treatment of during follow-up after discontinuation of treatment or (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment during follow-up after discontinuation of study treatment. Estimated rate of PFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
(Accelerated Phase/Blast Crisis) AP/BC was defined as time between randomization and either (1) (Chronic Myeloid Leukemia) CML-related death (if death was primary reason for discontinuation) or (2) progression to AP or BC (during treatment). Estimated rate of AC/BC was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
OS was defined as time between randomization and death due to any cause during study treatment or during follow-up after discontinuation of treatment. Estimated rate of OS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
Duration of MMR (months) = (date of first confirmed loss or censoring - date of MMR + 1 ) / 30.4375. Estimated rate of duration of first MMR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
Duration of CCyR was defined as the time between date of CCyR and the earliest of either (1) loss of CCyR OR (2) (Chronic Myeloid Leukemia) CML-related death or progression to (Accelerated Phase/Blast Crisis) AP/BC during study treatment. Estimated rate of duration of first CCyR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Mean Actual Dose Intensity Per Day
The mean actual dose intensity per day from start of treatment up to last dose or discontinuation was evaluated up to Month 36. Actual dose intensity (mg/day) = total dose/time on treatment (periods of zero dose are included)
Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12
Imatinib PK trough plasma concentration (Cmin) was defined as any pre-dose Imatinib plasma concentration
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
A Landmark Kaplan-Meier analysis was performed for PFS at 42 months by MMR status at 6, 12, and 18 months to investigate their prognostic value.
Time to First Complete Molecular Response (CMR)]
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.
Number of Participants With the Effect of Imatinib on the Diabetic Participants With Known Concomitant Type II Diabetes

Full Information

First Posted
July 27, 2005
Last Updated
January 5, 2012
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00124748
Brief Title
Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)
Acronym
TOPS
Official Title
A Randomized Open-label Study of 400 mg Versus 800 mg of Imatinib Mesylate in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Using Molecular Endpoints.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Terminated
Why Stopped
This study was prematurely discontinued because no improvement was observed in the 800mg dose compared to 400mg dose
Study Start Date
June 2005 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
This study investigated the safety and efficacy of 400mg Versus 800mg imatinib in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Chronic Phase
Keywords
CML, Philadelphia positive, Bcr-abl, imatinib mesylate, Chronic myeloid leukemia (CML) in chronic phase

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Imatinib 400 mg
Arm Type
Experimental
Arm Description
Oral dose of 400mg Imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.
Arm Title
imatinib 800 mg
Arm Type
Experimental
Arm Description
Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.
Intervention Type
Drug
Intervention Name(s)
Imatinib mesylate
Other Intervention Name(s)
STI571, Gleevec, Glivec
Intervention Description
Imatinib is packaged in bottles as 100mg and 400mg tablets
Primary Outcome Measure Information:
Title
Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months
Description
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
Description
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).
Time Frame
24, 36 and 42 months
Title
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
Description
Cytogenetic response (CyR)is the percentage of Philadelphia chromosome positive metaphases (among at least 20 metaphase cells in bone marrow (BM)) with Complete Cytogenetic Response (CCyR) being 0 percent.
Time Frame
12, 24, 36, 42 months
Title
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
Description
Complete Hematologic Response (CHR) is where all of the following criteria must be present for ≥4 weeks: White Blood Cell (WBC) count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) < 5% in PB and No evidence of extramedullary involvement.
Time Frame
12, 24, 36, and 42 months
Title
Percentage of Patients With Undetectable Levels of Bcr-Abl (A Fusion Gene of the Breakpoint Cluster Region [Bcr] Gene and Abelson Proto-oncogene [Abl] Genes) Transcripts
Description
"Undetectable levels" or Complete molecular response is defined as Bcr-Abl ratio (%) on international scale (IS) <= 0.0032% (≥ 4.5 log reduction of BCR-Abl transcripts from a standardized baseline).
Time Frame
12 , 24, 36 and 42 months
Title
Time to First Major Molecular Response
Description
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally). Time to MMR (months) = (date of first MMR or censoring - date of randomization + 1) / 30.4375. Time to first MMR was evaluated using the Kaplan-Meier method
Time Frame
42 months overall
Title
Time to First Complete Cytogenetic Response
Description
Cytogenetic response (CyR) is the percentage of Philadelphia positive metaphases (among at least 20 metaphase cells in Bone Marrow) with Complete Cytogenetic Response (CCyR) being 0 percent. Time to CCyR (months) = (date of first CCyR or censoring - date of randomization + 1) / 30.4375. Time to first CCyR was evaluated using the Kaplan-Meier method.
Time Frame
60 months overall
Title
Time to First Complete Hematological Response (CHR)]
Description
Complete Hematological Response (CHR) is defined is where all of the following criteria must be present for ≥4 weeks: White Blood Cell (WBC) count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in Peripheral Blood (PB), (Myelocytes + metamyelocytes) < 5% in PB and No evidence of extramedullary involvement. Time to CHR (months) = (date of first CHR or censoring - date of randomization + 1) / 30.4375. Time to first CHR was evaluated using the Kaplan-Meier method.
Time Frame
60 months overall
Title
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
Description
EFS on treatment was defined as time between randomization and either (1) death due to any cause during study treatment, (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment, (3) loss of complete hematological response (CHR), or (4) loss of major cytogenic response (MCyR) while on treatment. Estimated rate of EFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Time Frame
60 months over all
Title
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
Description
PFS on study which was defined as time between randomization and either (1) death due to any cause on treatment of during follow-up after discontinuation of treatment or (2) progression to accelerated phase (AP) or blast crisis (BC) on treatment during follow-up after discontinuation of study treatment. Estimated rate of PFS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Time Frame
60 months over all and follow up period
Title
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
Description
(Accelerated Phase/Blast Crisis) AP/BC was defined as time between randomization and either (1) (Chronic Myeloid Leukemia) CML-related death (if death was primary reason for discontinuation) or (2) progression to AP or BC (during treatment). Estimated rate of AC/BC was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Time Frame
60 months over all and follow up period
Title
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
Description
OS was defined as time between randomization and death due to any cause during study treatment or during follow-up after discontinuation of treatment. Estimated rate of OS was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Time Frame
60 months over all and follow up period
Title
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
Description
Duration of MMR (months) = (date of first confirmed loss or censoring - date of MMR + 1 ) / 30.4375. Estimated rate of duration of first MMR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Time Frame
From First major molecular response to first confirmed loss or censoring
Title
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
Description
Duration of CCyR was defined as the time between date of CCyR and the earliest of either (1) loss of CCyR OR (2) (Chronic Myeloid Leukemia) CML-related death or progression to (Accelerated Phase/Blast Crisis) AP/BC during study treatment. Estimated rate of duration of first CCyR was analyzed by Kaplan-Meier estimate (percent probability and 95% Confidence interval).
Time Frame
From first complete cytogenetic response to first confirmed loss or censoring
Title
Mean Actual Dose Intensity Per Day
Description
The mean actual dose intensity per day from start of treatment up to last dose or discontinuation was evaluated up to Month 36. Actual dose intensity (mg/day) = total dose/time on treatment (periods of zero dose are included)
Time Frame
start of treatment to Month 36
Title
Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12
Description
Imatinib PK trough plasma concentration (Cmin) was defined as any pre-dose Imatinib plasma concentration
Time Frame
Month 12
Title
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
Description
A Landmark Kaplan-Meier analysis was performed for PFS at 42 months by MMR status at 6, 12, and 18 months to investigate their prognostic value.
Time Frame
42 months
Title
Time to First Complete Molecular Response (CMR)]
Description
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.
Time Frame
48 months overall
Title
Number of Participants With the Effect of Imatinib on the Diabetic Participants With Known Concomitant Type II Diabetes
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis) Diagnosis of chronic myelogenous leukemia (CML) in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Breakpoint cluster region gene-abelson proto-oncogene (Bcr-Abl) Documented chronic phase CML Adequate end organ function as defined by: total bilirubin < 1.5 x Upper Limit of Normal (ULN) Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x ULN creatinine < 1.5 x ULN Exclusion Criteria: Patients in late chronic phase, accelerated phase, or blastic phase are excluded Patients who have received other investigational agents Patients who received Gleevec/Glivec for any duration prior to study entry, with the exception of those patients successfully completing [CSTI571A2107 (NCT00428909)] study immediately prior to the participation in this study Patient received any treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes,chronic renal disease) Patient previously received radiotherapy to ≥ 25% of the bone marrow Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥ 3 Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment Other protocol-defined inclusion/exclusion criteria applied.
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
University of South Alabama
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36693
Country
United States
Facility Name
Alta Bates Comprehsenive Cancer Center
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
University of Miami
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
South Bay Oncology Hematology Partners
City
Campbell
State/Province
California
ZIP/Postal Code
95008
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Osler Medical Inc.
City
Melbourne
State/Province
Florida
ZIP/Postal Code
32901
Country
United States
Facility Name
Advanced Medical Specialists
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Integrated Community Oncology Network
City
Orange Park
State/Province
Florida
ZIP/Postal Code
32073
Country
United States
Facility Name
Hematology-Oncology Associates, P.A.
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32501
Country
United States
Facility Name
Palm Beach Cancer Institute
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
233401
Country
United States
Facility Name
Palm Beach Cancer Institute
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Cancer Research Center of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Blood and Marrow Institutw
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
Indiana Blood and Marrow Transplant
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
University of Iowa Hospitals & Clinic
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kentucky - C201 Clinic
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Lousville Oncology, Clinical Research Program M-25
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Jayne S. Gurtler, MD, Laura A. Brinz, MD & Angelo Russo, MD
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Hematology and Oncology Specialists
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
LSU Health Science Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
LSU Health Scine Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130
Country
United States
Facility Name
St. Agnes Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Great Lakes Cancer Institute
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
U of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
San Juan Oncology Associates
City
Farmington
State/Province
New Mexico
ZIP/Postal Code
87401
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cancer Center of the Carolinas
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University Hospitals of Cleveland, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Kaiser Permanente Northwest Region Oncology/Hemacology
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Kaiser Permanente Northwest Region
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Western Pennsylvania Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
University of Pittsburg, Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
MUSC Hollings Cancer Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Cancer Center of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Cancer Centers of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
The Jones Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
UT Southwestern Harold C. Simmons Comprehensive Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas / MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Virgina Cancer Center, UVA Division of Hematology & Oncology
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Novartis Investigative Site
City
Buenos Aires
Country
Argentina
Facility Name
Novartis Investigative Site
City
La Plata
Country
Argentina
Facility Name
Novartis Investigative Site
City
St. Leonards
State/Province
New South Wales
Country
Australia
Facility Name
Novartis Investigative Site
City
Waratah
State/Province
New South Wales
Country
Australia
Facility Name
Novartis Investigative Site
City
Westmead
State/Province
New South Wales
Country
Australia
Facility Name
Novartis Investigative Site
City
Herston
State/Province
Queensland
Country
Australia
Facility Name
Novartis Investigative Site
City
Woolloongabba
State/Province
Queensland
Country
Australia
Facility Name
Novartis Investigative Site
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Novartis Investigative Site
City
East Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Novartis Investigative Site
City
Fitzroy
State/Province
Victoria
Country
Australia
Facility Name
Novartis Investigative Site
City
Frankston
State/Province
Victoria
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
Country
Australia
Facility Name
Novartis Investigative Site
City
Prahran
State/Province
Victoria
Country
Australia
Facility Name
Novartis Investigative Site
City
South Brisbane
Country
Australia
Facility Name
Novartis Investigative Site
City
Campinas
Country
Brazil
Facility Name
Novartis Investigative Site
City
Calgary
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
Country
Canada
Facility Name
Novartis Investigative Site
City
Ottawa
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
Country
Canada
Facility Name
Novartis Investigative Site
City
Bologna
Country
Italy
Facility Name
Novartis Investigative Site
City
Firenze
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
Roma
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
24859364
Citation
Branford S, Yeung DT, Parker WT, Roberts ND, Purins L, Braley JA, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Donaldson Z, Leong M, Fletcher L, Seymour JF, Grigg AP, Ross DM, Hughes TP. Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood. 2014 Jul 24;124(4):511-8. doi: 10.1182/blood-2014-03-566323. Epub 2014 May 23.
Results Reference
derived
PubMed Identifier
23515925
Citation
Branford S, Yeung DT, Ross DM, Prime JA, Field CR, Altamura HK, Yeoman AL, Georgievski J, Jamison BA, Phillis S, Sullivan B, Briggs NE, Hertzberg M, Seymour JF, Reynolds J, Hughes TP. Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML. Blood. 2013 May 9;121(19):3818-24. doi: 10.1182/blood-2012-10-462291. Epub 2013 Mar 20.
Results Reference
derived
PubMed Identifier
22315495
Citation
Guilhot F, Hughes TP, Cortes J, Druker BJ, Baccarani M, Gathmann I, Hayes M, Granvil C, Wang Y. Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial. Haematologica. 2012 May;97(5):731-8. doi: 10.3324/haematol.2011.045666. Epub 2012 Feb 7.
Results Reference
derived
Links:
URL
http://www.novartisclinicaltrials.com
Description
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Learn more about this trial

Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)

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