Clinical Trial Results:
An Extension to a Phase II Study to Determine the Safety and Anti-Leukemic Effects of STI571 in Adult Patients With Philadelphia Chromosome Positive Leukemia Including Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Accelerated Phase Chronic Myeloid Leukemia
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Summary
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EudraCT number |
2005-001381-14 |
Trial protocol |
IT |
Global end of trial date |
23 Sep 2013
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Results information
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Results version number |
v3(current) |
This version publication date |
17 Oct 2021
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First version publication date |
05 Jul 2018
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Other versions |
v1 , v2 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CSTI571A0109E2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00171249 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Novartis Pharmaceuticals, Novartis Pharmaceuticals, +41 61-324-1111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma, +41 61-324-1111,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Sep 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Sep 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The objectives of Part 1 of the study were:
-To determine the rate of hematologic response (HR) lasting >/= 4 weeks in subjects iwth Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the accelerated phase (AP).
-To evaluate duration of HR, overall survival, cytogenetic response (CyR), time to blast crisis in CML patients in the AP, improvement of symptomatic parameters, tolerability and safety of STI571 treatment.
The objective of the extenstion (Part 2) was:
-To enable patients to have access to study drug and continue study treatment and to decrease data collection to include only overall survival and serious adverse events.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Aug 1999
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 28
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Country: Number of subjects enrolled |
France: 20
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Country: Number of subjects enrolled |
Germany: 52
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Country: Number of subjects enrolled |
United Kingdom: 34
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Country: Number of subjects enrolled |
Switzerland: 7
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Country: Number of subjects enrolled |
United States: 152
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Worldwide total number of subjects |
293
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EEA total number of subjects |
134
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
228
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From 65 to 84 years |
64
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85 years and over |
1
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Recruitment
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Recruitment details |
This multicenter study was carried out in the following countries (number of centers): France (2 ), Germany (4), Italy (2), UK (1), Switzerland (1) and USA (4). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
For Part 1 of the study, patients were screened over a 1- week period. Patients completing extension visit 5 (i.e., visit E5) or remaining on study treatment up to and including 31-Jul-2004, and fulfilling all requirements outlined for the End of Study Visit on STI 109 extension protocol #1 were eligible to participate in extension protocol #2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Accelerated phase chronic myeloid/myelogenous leukemia 400 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with accelerated phase chronic myeloid/myelogenous leukemia received STI571 400 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 400 mg
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Investigational medicinal product code |
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Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 400 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 400 mg may have had the dose increased to 600 mg. The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Arm title
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Lymphoid blast crisis 400 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with lymphoid blast crisis received STI571 400 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 400 mg
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Investigational medicinal product code |
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Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 400 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 400 mg may have had the dose increased to 600 mg. The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Arm title
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Acute lymphoblastic leukemia 400 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with acute lymphoblastic leukemia received STI571 400 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 400 mg
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 400 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 400 mg may have had the dose increased to 600 mg. The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Arm title
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Accelerated phase chronic myeloid/myelogenous leukemia 600 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with accelerated phase chronic myeloid/myelogenous leukemia received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 600 mg
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Investigational medicinal product code |
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Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 600 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 600 mg may have had the dose increased to 800 mg (administered as 400 mg b.i.d.). The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Arm title
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Lymphoid blast crisis 600 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with lymphoid blast crisis received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 600 mg
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Investigational medicinal product code |
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Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 600 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 600 mg may have had the dose increased to 800 mg (administered as 400 mg b.i.d.). The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Arm title
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Acute lymphoblastic leukemia 600 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with acute lymphoblastic leukemia received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 600 mg
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 600 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 600 mg may have had the dose increased to 800 mg (administered as 400 mg b.i.d.). The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Arm title
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Acute myeloid/myelogenous leukemia 600 mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Patients with acute myeloid/myelogenous leukemia received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
STI571 600 mg
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Investigational medicinal product code |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Other name |
Glivec, Gleevec
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Pharmaceutical forms |
Capsule, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg, 50 mg, and 100 mg capsules, once daily (QD) with 250 ml of water after breakfast, in a combination to achieve a 600 mg daily dose. As per Extension protocol, STI571 was supplied as tablets instead of capsules. Patients continued to use capsules until the supply of capsules was finished and were supplied with tablets. The capsules and tablets are bioequivalent.
Subjects who were resistant or relapsed while receiving treatment with STI571 at 600 mg may have had the dose increased to 800 mg (administered as 400 mg b.i.d.). The decision to dose-escalate was made by the investigator and the sponsor on a case by case basis.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
All patients, all doses | |||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Accelerated phase chronic myeloid/myelogenous leukemia 400 mg
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Reporting group description |
Patients with accelerated phase chronic myeloid/myelogenous leukemia received STI571 400 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Reporting group title |
Lymphoid blast crisis 400 mg
|
||
Reporting group description |
Patients with lymphoid blast crisis received STI571 400 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Reporting group title |
Acute lymphoblastic leukemia 400 mg
|
||
Reporting group description |
Patients with acute lymphoblastic leukemia received STI571 400 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Reporting group title |
Accelerated phase chronic myeloid/myelogenous leukemia 600 mg
|
||
Reporting group description |
Patients with accelerated phase chronic myeloid/myelogenous leukemia received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Reporting group title |
Lymphoid blast crisis 600 mg
|
||
Reporting group description |
Patients with lymphoid blast crisis received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Reporting group title |
Acute lymphoblastic leukemia 600 mg
|
||
Reporting group description |
Patients with acute lymphoblastic leukemia received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Reporting group title |
Acute myeloid/myelogenous leukemia 600 mg
|
||
Reporting group description |
Patients with acute myeloid/myelogenous leukemia received STI571 600 mg until death, the development of intolerable toxicity, or the investigator felt it was no longer in the patient’s best interest to continue therapy, whichever came first. | ||
Subject analysis set title |
Accelerated phase chronic myeloid/myelogenous leukemia
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This set includes patients who received either dose of STI571.
|
||
Subject analysis set title |
Lymphoid blast crisis
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This set includes patients who received either dose of STI571.
|
||
Subject analysis set title |
Acute lymphoid leukemia
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This set includes patients who received either dose of STI571.
|
||
|
|||||||||||||
End point title |
Percentage of Participants With Hematologic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia [1] [2] | ||||||||||||
End point description |
Hematologic response was evaluated from hematology measurements in the peripheral blood (PB) and bone marrow (BM) and assessments of extramedullary leukemic involvement (EMD) at physical examination. Response was defined as complete hematologic remission (CHR), no evidence of leukemia (NEL), or return to chronic phase (RTC).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 3 years after start of treatment
|
||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: no statistic analysis was performed [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistic analysis were performed |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With Cytogenetic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia [3] | ||||||||||||
End point description |
Bone marrow (BM) cytogenetic analysis was required at baseline, after 12 weeks (visit 22) and after 24 weeks (visit 28) to evaluate Ph chromosome positivity. In several participants, this was also done after 4 and 8 weeks. Based on the percentage of Philadelphia chromosome positive (Ph+) cells = (positive cells/examined cells)x100, at each BM assessment the cytogenetic response was classified as: Complete, 0% Ph+ cells; Partial, >0 - 35% Ph+ cells; Minor, >35 - 65% Ph+ cells; Minimal, >65 - 95% Ph+ cells; None, >95% Ph+ cells; Not done: <20 metaphases were examined and/or response could not be assigned. Cytogenetic response was defined as confirmed complete or partial response. A BM sample was considered as assessable for cytogenetic response only if it contained ≥20 metaphases. However, an assessment of partial response was retained in a sample with <20 metaphases when it was immediately preceded or followed by a complete or partial response in another sample with ≥20 metaphases.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 3 years after start of treatment
|
||||||||||||
| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistic analysis were performed |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||
End point title |
Time to Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia [4] | ||||||||||||||||||
End point description |
Time to response was defined for all participants as the time until first documented response (which was confirmed ≥4 weeks later).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 3 years after start of treatment
|
||||||||||||||||||
| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistic analysis were performed |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [5] - N for hematologic response = 50; N for cytogenetic response = 15 [6] - N for hematologic response = 118; N for cytogenetic response = 49 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Duration of Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia [7] | ||||||||||||||||||
End point description |
Duration of response was defined as the time between first documented response (which was confirmed ≥4 weeks later) and the earliest date of the following: loss of response (when any of the criteria for response were no longer fulfilled); progression to blast crisis (≥30% blasts in peripheral blood or bone marrow, extramedullary involvement other than liver/spleen enlargement); discontinuation due to adverse event, laboratory abnormality, unsatisfactory therapeutic effect or death.
999999= NA: Upper limit of 95% CI was not estimable due to censored data
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 3 years after start of treatment
|
||||||||||||||||||
| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistic analysis were performed |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [8] - N for hematologic response = 50; N for cytogenetic response = 15 [9] - N for hematologic response = 118; N for cytogenetic response = 49 |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Time to Progression to Blast Crisis in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia [10] | ||||||||||||
End point description |
Progression to blast crisis was defined as ≥30% blasts in peripheral blood or bone marrow or as extramedullary involvement other than liver or spleen enlargement.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 3 years after start of treatment
|
||||||||||||
| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistic analysis were performed |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Kaplan-Meier Estimates of Overall Survival by Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
To evaluate overall survival, all patients were to be followed after the last dose of study drug every month for the first three months and thereafter every three months until death. Overall survival was calculated for all patients as the time between start of treatment and death due to any reason. The time was censored at the date of last contact for patients who discontinued treatment and were in survival follow-up. For patients without survival follow-up information, the time was censored at last available visit / treatment date.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132, 144, and 156 months after start of treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Overall Survival by Dose in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia [11] | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
To evaluate overall survival, all participants were followed after the last dose of study drug every month for the first three months and thereafter every three months until death. Overall survival was calculated for all participants as the time between start of treatment and death due to any reason. The time was censored at the date of last contact for participants who discontinued treatment and were in survival follow-up. For participants without survival follow-up information, the time was censored at last available visit/treatment date.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 months after start of treatment
|
|||||||||||||||||||||||||||||||||||||||||||||
| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: no statistic analysis was performed |
||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information [1]
|
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Timeframe for reporting adverse events |
Safety information provided in the final CSR is based on SAEs reported in the safety (ARGUS) database. All AEs reported in the clinical database had been included in the CSR based on data cut-off of core document.
|
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Adverse event reporting additional description |
Information about all serious adverse events was collected on the SAE form and recorded in
the safety database only. To ensure patient safety each serious adverse event also had to be
reported to Novartis within 24 hours of learning its occurrence.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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Reporting groups
|
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Reporting group title |
STI571 all doses
|
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Reporting group description |
The only data available during this part of the trial are data from spontaneous reporting furnished to Novartis externally. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: AEs were not collected separately for each disease and dose groups of participants. The data has been reported as originally produced by the team at the time of reporting. We have exhausted all efforts to locate additional data; therefore, no additional data is available to report or modify what has previously been reported. No other non-serious AEs were collected during extension phase within clinical database. |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
05 Oct 1999 |
The main changes are summarized as follows:
- Recruitment to the three exploratory disease groups: Ph+ CML in LBC, Ph+ ALL, Ph+AML, was put on hold.
- Patients with total serum bilirubin </= 3x the ULN were allowed to enter the study.
- It was decided to limit the number of patients treated at 400 mg o.d. in this study, and to add a cohort at 600 mg o.d.
- Dose escalation from 400 to 600 mg daily for patients who became resistant or relapsed while receiving STI571 treatment was allowed.
- Trough plasma concentrations of STI571 on days 8 and 28 were to be determined in patients from US centers only.
- Patients were allowed to be followed at the referral center after a minimum period of two months of follow-up at the study center.
- Fluorescence in situ hybridisation (FISH) analysis was to be performed on bone marrow samples with less than 20 identified metaphases for cytogenetics. |
||
21 Dec 1999 |
The main changes are summarized as follows:
- Additional patients with CML in AP were to be recruited onto the study at the 600 mg o.d. dose level, after significant initial response rates had been observed in this population.
- Patients with CML in AP were to be included only if they had never been in the blastic phase of the disease.
- The adult Ph+ ALL and AML groups were to be re-opened for accrual, after analysis of data from the Phase 1 study showed significant response rates in these groups.
- Accrual into the CML LBC disease group was discontinued.
- Patients receiving therapy with drugs known to significantly affect gastric pH were allowed to enter the study.
- Patients with disease progression while on STI571 treatment at a dose of 600 mg o.d. could have the dose increased to 800 mg, administered as 400 mg b.i.d., since no drug-related SAEs had been recorded in the cohort of patients receiving this dose in the Phase I study.
- The dose reduction steps for non-hematological toxicity were simplified.
- Procedures for management of grade 4 neutropenia were modified.
- The evaluation of PK of STI571 was extended, by implementing a population PK study which included patients in CML in AP only.
- The statistical section of the protocol was revised. |
||
30 Aug 2000 |
The main changes are summarized as follows:
- Patients were allowed to take STI571 immediately before and during meals, following results from a study, which showed that the effect of food on the bioavailability of STI571 was minimal.
- During Part 2 of the study only, the monthly requirement for evaluation of the patient at the study center was changed to 3-monthly during the first 6 months and 4-monthly thereafter. The visits could be conducted at the referral site.
- The supply of STI571 to patients was changed to monthly during study Part 1, 3-monthly during the first 6 months of Part 2 and 4-monthly thereafter. |
||
13 Mar 2008 |
The main changes are summarized as follows:
- Follow up study visits will be decreased from every six months to every year (±3 months) at which time a yearly supply of study drug will be dispensed.
- For discontinued patients, survival information data collection will be decreased from every six months to every year (±3months) until death, or for a period of up to a total of five years, inclusive from the date the patient commenced the extension protocol, whichever is longer.
- The addition of a new section to include protocol deviation language that states that under no circumstances are protocol deviations allowed.
- Patients will be discontinued if they do not adhere to the study requirements.
- Study drug will only be shipped directly to the investigational sites.
- Study drug STI571 tablets will be used instead of capsules. |
||
17 Aug 2012 |
This amendment introduced the following changes:
Section 1, Introduction
- Addition of statement to reflect that the study will be closed following the final visit of patients. Patients that are currently benefiting from the study medication can enroll in the roll-over protocol (CSTI571A2406) and receive the same dose of imatinib.
- Addition of statement to reflect that the study will be closed following the final visit of patients. Patients that are currently benefiting from the study medication can enroll in the roll-over protocol (CSTI571A2406) and receive the same dose of imatinib.
Section 3.3.1, Dispensing of Drug
- Addition of statement to reflect that study treatment will not be dispensed to the patients at their final visit. On-going patients that are currently benefiting from the treatment with imatinib as determined by the investigator, will continue to have access to imatinib in the roll-over protocol (CSTI571A2406).
Section 3.4.1, Visit Schedule
- The evaluation schedule is updated to reflect that once the roll-over protocol is approved at the study site patients will have their final visit. No study treatment will be dispensed to the patient at this final visit. Patients will need to sign an informed consent (amendment 2) as part of their final visit on the parent study informing them about these changes.
Section 3.4.2.1, Overall Survival
- Addition of statement for patients that have discontinued the study treatment no further follow-up visits are to be conducted.
Section 5, Data Management
- Addition of statement to reflect that the investigator must enter the information for patients who have discontinued the study drug as well as for those patients who will enroll in the roll-over protocol. For those patients given the opportunity to enroll in the roll-over protocol the Comments CRF is to document “Patient to enroll in Study CSTI571A2406” or similar wording. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results. | |||
