Approval Probability
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STI571 · 7 trials · 15 indications
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.
| Arm | Type | Description |
|---|---|---|
| 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 |
| Name | Type | Description |
|---|---|---|
| STI571 (400 mg/day; or 800 mg/day) | DRUG | - |
| 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...
STI571 is used for chronic myeloid leukemia that is BCR-ABL positive, including Philadelphia chromosome positive chronic myeloid leukemia. It is also studied for systemic sclerosis, scleroderma, third line gastrointestinal stromal tumors, and prostatic neoplasms. The drug is in clinical development for these conditions.
STI571 is developed by Novartis AG, a company traded on the New York Stock Exchange under the ticker NVS. Novartis is the sponsor of the clinical trials evaluating this small molecule drug.
STI571 is in Phase 1 clinical development. It has completed Phase 2 and Phase 3 trials for chronic myeloid leukemia, and a Phase 1 trial for third line gastrointestinal stromal tumors is also completed. The drug remains investigational and is not approved.
STI571 has completed several clinical trials. NCT00171223 is a Phase 2 extension study in chronic myeloid leukemia with 532 participants. NCT00511303 is a Phase 2 study in Philadelphia chromosome positive chronic myeloid leukemia. NCT01468688 is a Phase 1 dose-finding study in third line GIST.
STI571 is also known as imatinib. Clinical trials reference both names, such as NCT00514488, which compares imatinib standard dose to high dose in chronic myeloid leukemia, and NCT01468688, which studies imatinib in combination for third line GIST.