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NCT00171249

An Extension Study to Determine the Safety and Anti-Leukemic Effects of Imatinib Mesylate in Adult Participants With Ph+ Leukemia

Completed Phase 2 Results posted Last updated 22 July 2021
What this trial tests

Phase 2 trial testing STI571 400 mg in Philadelphia Positive Chronic Myeloid Leukemia in 293 participants. Completed in 23 September 2013.

Timeline
9 August 1999
Primary endpoint
23 September 2013
23 September 2013

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment293
Start date9 August 1999
Primary completion23 September 2013
Estimated completion23 September 2013
Sites12 locations across France, Italy, United Kingdom, Germany, United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Philadelphia Positive Chronic Myeloid Leukemia or Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Hematologic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia Primary · Up to 3 years after start of treatment

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).

GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg64.953.2 – 75.5
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg74.767.2 – 81.3
Percentage of Participants With Cytogenetic Response in Accelerated Phase Chronic Myeloid/Myelogenous Leukemia Secondary · Up to 3 years after start of treatment

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 n

GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg14.37.4 – 24.1
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg24.718.2 – 32.2
Time to Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia Secondary · Up to 3 years after start of treatment

Time to response was defined for all participants as the time until first documented response (which was confirmed ≥4 weeks later).

Hematologic response
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg0.950.95 – 1.1
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg0.990.99 – 1
Cytogenetic response
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg2.831.9 – 5.6
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg2.962.8 – 5.5
Duration of Response in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia Secondary · Up to 3 years after start of treatment

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.

Hematologic response
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg16.4610.4 – 27.4
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg28.8125.7 – NA
Cytogenetic response
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg26.286.6 – NA
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg27.6315.9 – NA
Time to Progression to Blast Crisis in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia Secondary · Up to 3 years after start of treatment

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.

GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg9.956.6 – 14.4
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg25.1318.1 – 29.8
Overall Survival by Disease Secondary · 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 months after start of treatment

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.

12 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia74.468.3 – 79.5
Lymphoid Blast Crisis12.50.7 – 42.3
Acute Lymphoid Leukemia10.43.8 – 20.9
Acute Myeloid/Myelogenous Leukemia00 – 0
24 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia58.852.2 – 64.8
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia8.32.7 – 18.2
Acute Myeloid/Myelogenous Leukemia00 – 0
36 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia4841.4 – 54.2
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia8.32.7 – 18.2
Acute Myeloid/Myelogenous Leukemia00 – 0
48 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia39.933.5 – 46.2
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia8.32.7 – 18.2
Acute Myeloid/Myelogenous Leukemia00 – 0
60 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia32.226.1 – 38.4
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia8.32.7 – 18.2
Acute Myeloid/Myelogenous Leukemia00 – 0
72 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia26.320.6 – 32.3
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia8.32.7 – 18.2
Acute Myeloid/Myelogenous Leukemia00 – 0
84 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia24.118.6 – 30.1
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia8.32.7 – 18.2
Acute Myeloid/Myelogenous Leukemia00 – 0
96 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia21.916.5 – 27.8
Lymphoid Blast Crisis00 – 0
Acute Lymphoid Leukemia5.61.2 – 15.2
Acute Myeloid/Myelogenous Leukemia00 – 0
Overall Survival by Dose in Participants With Accelerated Phase Chronic Myeloid/Myelogenous Leukemia Secondary · 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, and 132 months after start of treatment

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.

12 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg64.552.6 – 74.1
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg79.171.9 – 84.7
24 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg44.332.9 – 55.1
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg65.757.7 – 72.6
36 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg34.924.4 – 45.7
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg54.246.0 – 61.6
48 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg28.018.4 – 38.5
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg45.637.6 – 53.2
60 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg23.714.7 – 33.9
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg36.228.6 – 43.9
72 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg18.610.5 – 28.5
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg29.922.6 – 37.5
84 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg15.27.8 – 24.8
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg28.321.2 – 35.9
96 months
GroupValue95% CI
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg11.85.4 – 21.0
Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg26.619.6 – 34.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 14 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

STI571
Serious: 20/293 (7%)
Deaths:

Serious adverse events (18 terms)

ReactionSystemSTI571
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DeathGeneral disorders
Subdural haematomaInjury, poisoning and procedural complications
Transfusion reactionInjury, poisoning and procedural complications
Breast cancer recurrentNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Haemorrhage intracranialNervous system disorders
Dementia Alzheimer's typeNervous system disorders
Bone painMusculoskeletal and connective tissue disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
OsteoporosisMusculoskeletal and connective tissue disorders
Clostridium difficile colitisInfections and infestations
Atypical mycobacterial infectionInfections and infestations
PneumoniaInfections and infestations

Most-reported serious reactions: Prostate cancer, Death, Subdural haematoma, Transfusion reaction, Breast cancer recurrent, Gastrointestinal neoplasm, Malignant neoplasm progression, Pulmonary haemorrhage.

Data from ClinicalTrials.gov NCT00171249 adverse events section.

Sponsor's own description

The objectives of Part 1 of the study were: * To determine the rate of hematologic response (HR) lasting ≥4 weeks in participants with 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 participants in the AP, improvement of symptomatic parameters, tolerability and safety of STI571 treatment. The objective of the extension (Part 2) was: -To enable participants to have access to study drug and continue study treatment and to decrease data collection to include only overall survival and serious adverse events.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Improving computational drug repositioning through multi-source disease similarity networks.
    Le DH. · · 2025 · cited 1× · PMID 40841559 · DOI 10.1038/s41598-025-04772-0

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