An Extension Study of the Safety and Anti-leukemic Effects of Imatinib Mesylate in Participants With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Blast Crisis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00171158
• Collaborator: (none)
• Enrollment: 260
• Locations: 10
• Arm: 1
• Actual Duration (Months): 164.9
• Patients Per Site: 26
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Philadelphia Chromosome Positive CML	Drug: imatinib mesylate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Extension to a Phase II Open-label Study to Determine the Safety and Anti-leukemic Effects of STI571 in Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Myeloid Blast Crisis
• Actual Study Start Date: Jul 26, 1999
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 22, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: imatinib mesylate; Other Names: Gleevec/Glivec

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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:

2. ≥ 30% blast in peripheral blood and /or bone marrow

3. by flow cytometry criteria

4. 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.

5. 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.

6. 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/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637
2	Dana Faber Institute	Boston	Massachusetts	United States	02115
3	MD Anderson Cancer Center	Houston	Texas	United States	77030
4	Novartis Investigative Site	Poitiers		France
5	Novartis Investigative Site	Frankfurt/Main		Germany
6	Novartis Investigative Site	Leipzig		Germany
7	Novartis Investigative Site	Mannheim		Germany
8	Novartis Investigative Site	Muenchen		Germany
9	Novartis Investigative Site	Bologna		Italy
10	Novartis Investigative Site	Monza		Italy

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00171158
• Other Study ID Numbers: CSTI571A0102E2; 2005-001380-61
• First Posted: Sep 15, 2005
• Last Update Posted: Jun 25, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Chronic Myelogenous Leukemia; CML; Philadelphia Chromosome; Blast crisis; Imatinib mesylate
• Additional relevant MeSH terms: Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Philadelphia Chromosome; Imatinib Mesylate

Study Results

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 Detail

The study enrolled 8 participants with myeloid blast crisis who completed their participation in Study CSTI571A0102E1.

Arm/Group Title	Imatinib Mesylate (STI571)
Arm/Group Description	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.
Period Title: Core Study
STARTED	260
COMPLETED	21
NOT COMPLETED	239
Period Title: Core Study
STARTED	8
COMPLETED	1
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Imatinib Mesylate (STI571)
Arm/Group Description	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.
Overall Participants	260
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	124 47.7%
Male	136 52.3%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	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.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) population included all participants who enrolled in the study.

Arm/Group Title	Imatinib Mesylate (STI571)
Arm/Group Description	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.
Measure Participants	260
Number [percentage of participants]	89.2 34.3%

2. Primary Outcome

Title	Overall Survival (by Month)
Description	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.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) population included all participants who enrolled in the study.

Arm/Group Title	Imatinib Mesylate (STI571)
Arm/Group Description	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.
Measure Participants	260
12 Months	32.7 12.6%
24 Months	18.7 7.2%
36 Months	15.4 5.9%
48 Months	14.5 5.6%
60 Months	9.1 3.5%
72 Months	8.4 3.2%
84 Months	7.5 2.9%
96 Months	7.5 2.9%
108 Months	7.5 2.9%
120 Months	6.6 2.5%
132 Months	5.5 2.1%
144 Months	5.5 2.1%
156 Months	5.5 2.1%

Adverse Events

Time Frame	Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to 14 years.
Adverse Event Reporting Description	After 31 July 2002 no safety data was collected in the clinical database and serious adverse events (SAEs) were reported in the safety database. No drug-related SAEs leading to discontinuation or drug-related deaths were reported after 31 July 2002 in the safety database.
Arm/Group Title	Imatinib Mesylate (STI571)
Arm/Group Description	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.
All Cause Mortality
	Imatinib Mesylate (STI571)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Imatinib Mesylate (STI571)
	Affected / at Risk (%)	# Events
Total	0/260 (0%)
Other (Not Including Serious) Adverse Events
	Imatinib Mesylate (STI571)
	Affected / at Risk (%)	# Events
Total	0/260 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.