Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as STI571, Glivec®, Gleevec®
Imatinib mesilate · 9 trials · 17 indications
Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.
The efficacy of oral STI571 in participants with systemic sclerosis is defined by an improvement in MRSS. Skin thickness was assessed clinically in each of 17 body areas and scored using a 0-3 scale, where 0= normal, 1= mild thickness, 2= moderate thickness, and 3= severe thickness (maximum score 51). A higher score indicates greater severity of the disease.
An AE is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to the study drug. An SAE is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, is medically significant, i.e., defined as an event that jeopardizes the patient or may require medical or surgical intervention to prevent one of the outcomes listed above.
Response was evaluated from bone marrow aspirates and biopsy samples. Bone marrow cytogenetic studies were performed every 3 months during the core phase of the study, then twice yearly, then annually to evaluate Philadelphia chromosome positive (Ph+). Cytogenetic response was defined as the best response the participant achieved during study. Based on the percentage of Ph+ cells = (positive cells/ examined cells) x100, at each BM assessment the cytogenetic response was classified as: Complete Cytogenetic Response (CCyR):, 0% Ph+ cells; Partial Cytogenetic Response (PCyR):, \>0 - 35% Ph+ cells; Minor: \>35 - 65% Ph+ cells; and Minimal: \>65 - 95% Ph+ cells, None: \>95 % Ph+ cells and Not done: \<20 metaphases were examined and/or response could not be assigned. Major Cytogenetic Response (MCyR) was defined as sum of the CCyR plus PCyR rates.
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).
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
An imaging technique (CT scan or MRI) determined tumor response according to RECIST criteria.
| Arm | Type | Description |
|---|---|---|
| imatinib (STI571) | EXPERIMENTAL | In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injection for 10 days every month. Maximum study duration was 11.5 years. |
| IFN-a+Ara-C | ACTIVE_COMPARATOR | In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years. |
| ST1571 | EXPERIMENTAL | Participants received ST1571 100 mg tablets, orally, once daily. Initiated at an oral dose of 200 mg/day for 4 weeks then titrated up to 400 mg/day for 2 weeks followed by 600 mg/day until Week 24, if well tolerated. |
| imatinib mesylate | EXPERIMENTAL | - |
| All Participants With Chronic Myeloid Leukemia | EXPERIMENTAL | Participants received STI571, capsules or tablets, orally, once a day at a dose of 400 mg. During the Core Phase of the study, participants received STI571 daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study, and they continued STI571 for as long as the therapy was beneficial or until death, intolerable toxicity or the decision to discontinue by the investigator, whichever came first. (Maximum duration on study was approximately 14 years). |
| Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 400 mg | EXPERIMENTAL | Participants with accelerated phase chronic myeloid/myelogenous leukemia received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| Lymphoid Blast Crisis 400 mg | EXPERIMENTAL | Participants with lymphoid blast crisis received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| Acute Lymphoblastic Leukemia 400 mg | EXPERIMENTAL | Participants with acute lymphoblastic leukemia received STI571 400 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| Accelerated Phase Chronic Myeloid/Myelogenous Leukemia 600 mg | EXPERIMENTAL | Participants with accelerated phase chronic myeloid/myelogenous leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| Lymphoid Blast Crisis 600 mg | EXPERIMENTAL | Participants with lymphoid blast crisis received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| Acute Lymphoblastic Leukemia 600 mg | EXPERIMENTAL | Participants with acute lymphoblastic leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| Acute Myeloid/Myelogenous Leukemia 600 mg | EXPERIMENTAL | Participants with acute myeloid/myelogenous leukemia received STI571 600 mg, orally, once daily, until death, the development of intolerable toxicity, or the investigator felt it was no longer in the participant's best interest to continue therapy, whichever came first. |
| STI571 (imatinib mesylate) and BKM120 | EXPERIMENTAL | The study will comprise of 2 parts. A dose escalation and a dose expansion part. Patients will receive increasing doses of BKM120 (40, 60, 80, 100 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. 35 patients will enter the expansion phase with 18 patients having a pharmacokinetic (PK) run-in period of 8 days receiving imatinib monotherapy or BKM120 monotherapy. |
| STI571+BKM120 | EXPERIMENTAL | BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy |
| STI571 monotherapy run-in | EXPERIMENTAL | STI571 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy |
| Gleevec/Glivec | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| STI571 (400 mg/day; or 800 mg/day) | DRUG | - |
| imatinib mesilate | DRUG | imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules. |
| interferon-alpha (INF-a) | DRUG | interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. |
| cytarabine (ARA-C) | DRUG | cytarabine 20 mg/m\^2/day (max 40 mg) SC for 10 days every month. |
| STI571 | DRUG | STI571 tablets taken orally once a day |
| STI571 (Glivec®) | DRUG | - |
| STI571 400 mg | DRUG | STI571 capsules and tablets |
| STI571 600 mg | DRUG | STI571 capsules and tablets |
| BKM120 | DRUG | BKM120 combination therapy |
Inclusion Criteria: 1. Age \>/=18 years 2. First chronic phase, less than 6 months of duration 3. High Sokal's risk 4. Ph positive 5. No previous treatment or hydroxiurea only. 6. Performance status (ECOG/WHO) \< 2 7. Written informed consent Exclusion Criteria: 1. Age \<18 2. Low or intermediate...
Imatinib mesilate is used in oncology for chronic myelogenous leukemia and for refractory desmoplastic small round cell tumors. It has been studied in newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia and in patients with refractory desmoplastic small round cell tumors. It is a small molecule developed by Novartis AG.
Imatinib mesilate targets ABL1, BCR, KIT, and PDGFRB. It is an inhibitor of these targets. By inhibiting the BCR-ABL fusion protein and related kinases such as KIT and PDGFRB, it interferes with signaling that drives the growth of the cancers it is studied in.
Imatinib mesilate is developed by Novartis AG, which trades under the ticker NVS. Novartis is the company associated with the clinical development of this small molecule oncology agent across the studied indications.
Imatinib mesilate has been evaluated in Phase 3 clinical development. The Phase 3 study in newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia has been completed. A Phase 1 study in refractory desmoplastic small round cell tumors has also been completed. It is an investigational agent in clinical development.
Imatinib mesilate has been studied in two completed trials. NCT00333840 was a Phase 3 active-controlled trial of imatinib versus interferon-alpha plus cytarabine in newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia, enrolling 1,106 patients. NCT00417807 was a Phase 1 trial in refractory desmoplastic small round cell tumors, enrolling 9 patients in Italy.