Leukemia, Myeloid, Chronic PhasePhase 3TOPSNCT00124748
Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)
A Phase 3 study testing Imatinib mesylate in people with Leukemia, Myeloid, Chronic Phase, run by Novartis Pharmaceuticals at 75 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia, Myeloid, Chronic Phase
- What is being tested?
- Imatinib mesylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 476 participants
- Where
- 75 sitesin 6 countries
- Study dates
- Jun 2005to Nov 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
Show all 14Show fewer
- 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.
Trial locations and contacts
75 sites in 6 countries.
75 sites in 6 countries
United States50 sites
St. Agnes Hospital
Baltimore, Maryland, 21229
Indiana Blood and Marrow Institutw
Beech Grove, Indiana, 46107
Indiana Blood and Marrow Transplant
Beech Grove, Indiana, 46107
Alta Bates Comprehsenive Cancer Center
Berkeley, California, 94704
University of Miami
Berkeley, California, 94704
Roswell Park Cancer Institute
Buffalo, New York, 14263
South Bay Oncology Hematology Partners
Campbell, California, 95008
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
University of Virgina Cancer Center, UVA Division of Hematology & Oncology
Charlottesville, Virginia, 22908
Rush University Medical Center
Chicago, Illinois, 60612
University Hospitals of Cleveland, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
UT Southwestern Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, 75390
Rocky Mountain Cancer Center
Denver, Colorado, 80218
Duke University Medical Center
Durham, North Carolina, 27710
San Juan Oncology Associates
Farmington, New Mexico, 87401
The Jones Clinic
Germantown, Tennessee, 38138
Cancer Center of the Carolinas
Greenville, North Carolina, 29615
Cancer Center of the Carolinas
Greenville, South Carolina, 29615
Cancer Centers of the Carolinas
Greenville, South Carolina, 29615
Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cancer Research Center of Hawaii
Honolulu, Hawaii, 96813
University of Texas / MD Anderson Cancer Center
Houston, Texas, 77030-4009
MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa Hospitals & Clinic
Iowa City, Iowa, 52242
Great Lakes Cancer Institute
Lansing, Michigan, 48910
University of Kentucky - C201 Clinic
Lexington, Kentucky, 40536
University of Kentucky
Lexington, Kentucky, 40536
UCLA Medical Center
Los Angeles, California, 90095
Lousville Oncology, Clinical Research Program M-25
Louisville, Kentucky, 40202
Osler Medical Inc.
Melbourne, Florida, 32901
Jayne S. Gurtler, MD, Laura A. Brinz, MD & Angelo Russo, MD
Metairie, Louisiana, 70006
Advanced Medical Specialists
Miami, Florida, 33176
U of Minnesota
Minneapolis, Minnesota, 55455
University of Minnesota
Minneapolis, Minnesota, 55455
University of South Alabama
Mobile, Alabama, 36693
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Hematology and Oncology Specialists
New Orleans, Louisiana, 70115
Integrated Community Oncology Network
Orange Park, Florida, 32073
Hematology-Oncology Associates, P.A.
Pensacola, Florida, 32501
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
University of Pittsburg, Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Kaiser Permanente Northwest Region Oncology/Hemacology
Portland, Oregon, 97227
Kaiser Permanente Northwest Region
Portland, Oregon, 97227
LSU Health Science Center
Shreveport, Louisiana, 71103
LSU Health Scine Center
Shreveport, Louisiana, 71130
Palm Beach Cancer Institute
West Palm Beach, Florida, 233401
Palm Beach Cancer Institute
West Palm Beach, Florida, 33401
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Australia12 sites
Novartis Investigative Site
Adelaide, South Australia
Novartis Investigative Site
East Melbourne, Victoria
Novartis Investigative Site
Fitzroy, Victoria
Novartis Investigative Site
Frankston, Victoria
Novartis Investigative Site
Herston, Queensland
Novartis Investigative Site
Parkville, Victoria
Novartis Investigative Site
Prahran, Victoria
Novartis Investigative Site
South Brisbane
Novartis Investigative Site
St Leonards, New South Wales
Novartis Investigative Site
Waratah, New South Wales
Novartis Investigative Site
Westmead, New South Wales
Novartis Investigative Site
Woolloongabba, Queensland
Italy6 sites
Novartis Investigative Site
Bologna
Novartis Investigative Site
Florence
Novartis Investigative Site
Milan
Novartis Investigative Site
Naples
Novartis Investigative Site
Orbassano
Novartis Investigative Site
Roma
Canada4 sites
Novartis Investigative Site
Calgary
Novartis Investigative Site
Montreal
Novartis Investigative Site
Ottawa
Novartis Investigative Site
Québec
Argentina2 sites
Novartis Investigative Site
Buenos Aires
Novartis Investigative Site
La Plata
About this study
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.
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.
- Conditions
- Leukemia, Myeloid, Chronic Phase
- Being tested
- Imatinib mesylate
- Keywords
- CML, Philadelphia positive, Bcr-abl, imatinib mesylate, Chronic myeloid leukemia (CML) in chronic phase
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib mesylateDrug
Also called STI571, Gleevec, Glivec
Imatinib is packaged in bottles as 100mg and 400mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Imatinib 400 mg | Experimental | 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. Receives: Drug: Imatinib mesylate |
| imatinib 800 mg | Experimental | 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. Receives: Drug: Imatinib mesylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 months
Secondary outcomes (18)
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).
Measured: 24, 36 and 42 months
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.
Measured: 12, 24, 36, 42 months
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.
Measured: 12, 24, 36, and 42 months
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).
Measured: 12 , 24, 36 and 42 months
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
Measured: 42 months overall
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.
Measured: 60 months overall
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.
Measured: 60 months overall
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).
Measured: 60 months over all
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).
Measured: 60 months over all and follow up period
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).
Measured: 60 months over all and follow up period
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).
Measured: 60 months over all and follow up period
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).
Measured: From First major molecular response to first confirmed loss or censoring
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).
Measured: From first complete cytogenetic response to first confirmed loss or censoring
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)
Measured: start of treatment to Month 36
Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12
Imatinib PK trough plasma concentration (Cmin) was defined as any pre-dose Imatinib plasma concentration
Measured: Month 12
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.
Measured: 42 months
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.
Measured: 48 months overall
Number of Participants With the Effect of Imatinib on the Diabetic Participants With Known Concomitant Type II Diabetes
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2005 (estimated)
- Study startJun 2005
- Primary completionNov 2010
- Study completionNov 2010
Why it stopped: This study was prematurely discontinued because no improvement was observed in the 800mg dose compared to 400mg dose
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, Chronic PhaseStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 476 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124748
- Sponsor's protocol ID
- CSTI571K2301
- Acronym
- TOPS
- Status last verified
- Jan 2012
- First submitted
- 27 Jul 2005
- Last updated
- 3 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 24859364Branford 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.
PubMed 23515925Guilhot 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.
PubMed 22315495
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00124748
- Acronym / sponsor ID
- TOPS / CSTI571K2301
- Conditions
- Leukemia, Myeloid, Chronic Phase
- Keywords
- CML, Philadelphia positive, Bcr-abl, imatinib mesylate, Chronic myeloid leukemia (CML) in chronic phase
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was prematurely discontinued because no improvement was observed in the 800mg dose compared to 400mg dose
- Enrolment
- 476 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 28 Jul 2005 (estimated)
- Results
- Posted 3 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Imatinib 400 mg | Experimental | Drug: Imatinib mesylateOral 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. |
| imatinib 800 mg | Experimental | Drug: Imatinib mesylatePatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib mesylateAlso: STI571, Gleevec, GlivecImatinib is packaged in bottles as 100mg and 400mg tablets | Drug | Imatinib 400 mg, imatinib 800 mg |
Primary outcome
Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months
Time frame: 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).
18 secondary outcomes
Percentage of Participants With Major Molecular Response (MMR) Rates at 24, 36, and 42 Months
Time frame: 24, 36 and 42 months
Percentage of Participants With Complete Cytogenetic Response (CCyR) Rate at 12, 24, 36, 42 Months
Time frame: 12, 24, 36, 42 months
Percentage of Participants With Complete Hematological Response (CHR) Rates at 12, 24, 36, and 42 Months
Time frame: 12, 24, 36, and 42 months
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
Time frame: 12 , 24, 36 and 42 months
Time to First Major Molecular Response
Time frame: 42 months overall
Time to First Complete Cytogenetic Response
Time frame: 60 months overall
Time to First Complete Hematological Response (CHR)]
Time frame: 60 months overall
Estimated Rate of Event Free Survival (EFS) in Two Treatment Arms
Time frame: 60 months over all
Estimated Rate of Progression Free Survival (PFS) in Two Treatment Arms
Time frame: 60 months over all and follow up period
Estimated Rate of Progression to Accelerated Phase (AC)/Blast Crisis (BC) in Two Treatment Arms
Time frame: 60 months over all and follow up period
Estimated Rate of Overall Survival (OS) in Two Treatment Arms
Time frame: 60 months over all and follow up period
Kaplan-Meier Estimates of Duration of First Major Molecular Response Until Confirmed Loss
Time frame: From First major molecular response to first confirmed loss or censoring
Kaplan-Meier Estimates of Duration of First Complete Cytogenetic Response (CCyR)
Time frame: From first complete cytogenetic response to first confirmed loss or censoring
Mean Actual Dose Intensity Per Day
Time frame: start of treatment to Month 36
Imatinib Pharmacokinetic Trough Plasma Concentration (Cmin) at Month 12
Time frame: Month 12
Estimated Rates of Progression Free Survival (PFS) on Treatment by Major Molecular Response (MMR)
Time frame: 42 months
Time to First Complete Molecular Response (CMR)]
Time frame: 48 months overall
Number of Participants With the Effect of Imatinib on the Diabetic Participants With Known Concomitant Type II Diabetes
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24859364Branford 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.
- Derived from this study: PubMed 23515925Branford 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.
- Derived from this study: PubMed 22315495Guilhot 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.
- Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
75 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Imatinib mesylate in people with Leukemia, Myeloid, Chronic Phase, run by Novartis Pharmaceuticals at 75 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 sites in United States, Australia, Italy, Canada, Argentina and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Major Molecular Response (MMR) Rates at 12 Months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00124748, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2012.