Philadelphia Chromosome Positive CML
Conditions
Keywords
Chronic Myelogenous Leukemia, CML, Philadelphia Chromosome, Blast crisis, Imatinib mesylate
Brief summary
This extension II study allowed for further follow-up of the disease under treatment with imatinib mesylate and allow the participants to continue to receive imatinib mesylate.
Interventions
DRUGimatinib mesylate
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Participants with Philadelphia chromosome positive chronic myelogenous leukemia (CML) in myeloid blast crisis (including both newly diagnosed and the participants who received prior therapy for accelerated or blastic phases), defined as either: 1. ≥ 30% blast in peripheral blood and /or bone marrow 2. by flow cytometry criteria 2\. To be categorized as newly diagnosed, participants with CML in blast crisis were not to have received specific therapy for CML accelerated or blast phases, with the exception of interferon-alpha or hydroxyurea. 3\. serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) not more than 3 times the upper limit of the normal range (ULN) (or not more than 5 times the ULN if clinically suspected leukemic involvement of the liver), serum creatinine concentration not more than 2 times the ULN, and total serum bilirubin level not more than 3 times the ULN at the laboratory where the analyses were performed. 4\. A negative pregnancy test in participants of childbearing potential.
Exclusion criteria
1. Participants with an eastern cooperative oncology group (ECOG) performance status score ≥ 3. 2. Participants previously treated for blast crisis were not to have received any of the following with respect to Day 1 of the study: busulfan within six weeks, interferon-alpha within 48-hours, hydroxyurea within 24-hours, homoharringtonine within 14 days, low-dose, moderate dose or high dose cytosine arabinoside within 7, 14 and 28 days respectively, anthracyclines, mitoxantrone, or etoposide within 21 days. 3. Participants receiving any hematopoietic stem cell transplantation within six weeks of Day 1. 4. Participants receiving any other investigational agents within 28 days of Day 1. 5. Participants with Grade 3/4 cardiac disease or any other serious concurrent medical conditions. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From first dose until death of the patient, up to 14 years. | Overall survival was defined as the number of events of death, expressed as a percentage, from the start of treatment to death, due to any reason. |
| Overall Survival (by Month) | From first dose until death of the patient, up to 14 years. | Overall survival was defined as the time between start of treatment and death due to any reason. Overall survival for the participants was calculated by Kaplan-Meier estimates per month. The time was censored at the date of last contact for participants who discontinued treatment and were in survival follow-up. |
Countries
France, Germany, Italy, United States
Participant flow
Recruitment details
The overall study was conducted at 28 investigative sites in 6 countries from 26 July 1999 to 22 April 2013. A total of 260 participants were enrolled in the core Study CSTI57A0102, of which 21 participants completed the treatment and were enrolled in the extension Study CSTI571A0102E1. 13 participants discontinued from the extension Study CSTI571A0102E1, and 8 of them were enrolled in the extension Study CSTI571A0102E2.
Pre-assignment details
The study enrolled 8 participants with myeloid blast crisis who completed their participation in Study CSTI571A0102E1.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate (STI571) Participants initially received STI571 capsules or tablets, orally, initially once daily (400 mg) or (600 mg). The dosage was escalated from 400 mg to 600 mg and from 600 mg to 800 mg, on an individual basis as per the investigator's judgement. Treatment continued until death, or the development of intolerable toxicity, or the participant was considered not to benefit from treatment, whichever came first. | 260 |
| Total | 260 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Core Study | Abnormal Laboratory Values | 2 |
| Core Study | Administrative problems | 1 |
| Core Study | Adverse event, non-fatal | 21 |
| Core Study | Consent withdrawn by subject | 6 |
| Core Study | Death | 27 |
| Core Study | Lost to Follow-up | 1 |
| Core Study | No longer required drug (BMT) | 14 |
| Core Study | Protocol Violation | 4 |
| Core Study | Unsatisfactory therapeutic effect | 163 |
| E2 Extension | Other | 7 |
Baseline characteristics
| Characteristic | Imatinib Mesylate (STI571) |
|---|---|
| Age, Continuous | 56 years |
| Sex: Female, Male Female | 124 Participants |
| Sex: Female, Male Male | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 260 |
| serious Total, serious adverse events | 0 / 260 |
Outcome results
Primary
Overall Survival
Overall survival was defined as the number of events of death, expressed as a percentage, from the start of treatment to death, due to any reason.
Time frame: From first dose until death of the patient, up to 14 years.
Population: The Intent-to-treat (ITT) population included all participants who enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate (STI571) | Overall Survival | 89.2 percentage of participants |
Primary
Overall Survival (by Month)
Overall survival was defined as the time between start of treatment and death due to any reason. Overall survival for the participants was calculated by Kaplan-Meier estimates per month. The time was censored at the date of last contact for participants who discontinued treatment and were in survival follow-up.
Time frame: From first dose until death of the patient, up to 14 years.
Population: The Intent-to-treat (ITT) population included all participants who enrolled in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 12 Months | 32.7 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 24 Months | 18.7 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 36 Months | 15.4 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 48 Months | 14.5 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 60 Months | 9.1 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 72 Months | 8.4 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 84 Months | 7.5 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 96 Months | 7.5 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 108 Months | 7.5 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 120 Months | 6.6 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 132 Months | 5.5 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 144 Months | 5.5 percentage of participants |
| Imatinib Mesylate (STI571) | Overall Survival (by Month) | 156 Months | 5.5 percentage of participants |