A Study of Midostaurin Efficacy and Safety in Newly Diagnosed Patients With FLT3-mutated AML
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03280030 |
|
Recruitment Status :
Completed
First Posted : September 12, 2017
Last Update Posted : February 24, 2023
|
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
This study will evaluate the efficacy and safety of midostaurin in combination with daunorubicin/cytarabine induction, high dose cytarabine consolidation and midostaurin single agent continuation therapy in newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia | Drug: Midostaurin Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 80 participants |
| Allocation: | Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II, Randomized, Double-blind, Multi-center, Placebo-controlled Study to Evaluate the Efficacy and Safety of Twice Daily Oral Midostaurin in Combination With Daunorubicin/Cytarabine Induction, High-dose Cytarabine Consolidation, and Midostaurin Single Agent Continuation Therapy in Newly Diagnosed Patients With FLT3-mutated Acute Myeloid Leukemia (AML). |
| Actual Study Start Date : | April 6, 2018 |
| Actual Primary Completion Date : | March 11, 2020 |
| Actual Study Completion Date : | November 14, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial acute myeloid leukemia with mutated CEBPA
Cytogenetically normal acute myeloid leukemia
Core binding factor acute myeloid leukemia
Drug Information available for:
Midostaurin
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Midostaurin
Patients will take study drug on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
|
Drug: Midostaurin
Midostaurin 50 mg [two 25 mg capsules] will be administered twice per day by mouth on day 8-21 during induction and consolidation phase; then continuously during continuation phase
Other Name: PKC412 |
|
Placebo Comparator: Placebo
Patients will take placebo on day 8-21 during induction and consolidation phase; then continuously during continuation phase.
|
Drug: Placebo
Placebo two capsules will be administered twice per day by mouth on day 8-21 during induction and consolidation phase ; then continuously during continuation phase. |
Primary Outcome Measures :
- Incidence of Safety Events (Part 1, Japan only) [ Time Frame: Day 21 of the first Consolidation cycle ]Incidence and severity of Safety Events, defined as death or serious adverse event leading to treatment discontinuation that occurs on or before Day 21 of the first Consolidation cycle. This is is determined by the Independent Safety Committee to be definitely or probably related to midostaurin.
- Event Free Survival (Part 2 - randomized, controlled) [ Time Frame: up to 3 years after last patient started treatment ]Event Free survival defined as the time from the date of randomization until an EFS event is observed. An EFS event is defined as a failure to obtain a CR within an induction 2, relapse after CR, or death due to any cause, whichever occurs first.
Secondary Outcome Measures :
- Overall Survival [ Time Frame: up to 3 years after last patient started treatment ]Overall survival defined as the time from the date of randomization to date of death due to any cause
- Complete Remission [ Time Frame: up to 3 years after last patient started treatment ]Complete Remission defined as the proportion of patients with a CR according to Chelson Criteria, at various timepoints
- Cumulative incidence of relapse (CIR) [ Time Frame: up to 3 years after last patient started treatment ]CIR (only for patients who have achieved CR after study treatment initiation), is measured from the date of first CR to relapse or death due to AML, whichever occurs first.
- Metabolite CGP52421 [ Time Frame: Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12 ]Evaluate the pharmacokinetic of major metabolite of midostaurin CGP52421
- Metabolite CGP62221 [ Time Frame: Induction 1 Cycle 1 Day 8, Day 11, Day 15, Day 18 and Day 21, Consolidation Cycle 1 Day 8, Day 21, Cycle 3 Day 8, Day 21 Prior to first cycle of continuation cycle 1, Continuation Cycle 5, Continuation Cycle 9 and Completion Cycle 12 ]Evaluate the pharmacokinetic of major metabolite of Midostaurin CGP62221.
- Quality of life (QoL) per European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 [ Time Frame: Screening, D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year ]EORTC)QLQ-C30 total score and functional scales scores as determined by the score and absolute change from baseline at each scheduled assessment.
- Quality of life (QoL) per Patient Global Impression of Change (PGIC) [ Time Frame: D21 of each cycle of Induction and Consolidation; D1 of each cycle of Continuation, at end of treatment and during the post treatment follow up every 4 months during the first year ]PGIC score determined frequencies and percentages by scheduled timepoint.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of AML (≥ 20% blasts in the bone marrow based on WHO 2016 classification). Patients with APL (acute promyelocytic leukemia) with PML-RARA are not eligible
- Documented presence of an ITD and/or TKD activating mutation in the FLT3 gene, as determined by analysis in a Novartis designated laboratory An exception will be patients who are enrolled into the part 1 in Japan, who may be treated with midostaurin irrespective of AML FLT3 genotype.
-
Patients must meet the following laboratory value criteria that indicate adequate organ function at the screening visit:
- Estimated creatinine clearance ≥ 30 ml/min
- Total bilirubin ≤ 1.5 x ULN, except in the setting of isolated Gilbert syndrome
- Aspartate transaminase (AST) ≤ 3.0 x ULN
- Alanine transaminase (ALT) ≤ 3.0 x ULN
- Suitability for intensive chemotherapy in the judgment of the investigator
Exclusion Criteria:
- Neurologic symptoms suggestive of CNS leukemia unless CNS leukemia has been excluded by a lumbar puncture. Patients with CSF fluid positive for AML blasts are not eligible
- Developed therapy-related AML after prior radiotherapy (RT) or chemotherapy for another cancer or disorder
- Known hypersensitivity to midostaurin, cytarabine or daunorubicin or to any of the excipients of midostaurin/placebo, cytarabine or daunorubicin
- Abnormal chest X-ray unless the abnormality represents a non-active, or non-clinically significant finding, such as scarring (subjects with controlled non active lung infection are eligible)
- Known impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin
- Cardiac or cardiac repolarization abnormality
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 4 months after stopping medication Other protocol-defined Inclusion/Exclusion criteria may apply.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03280030
Locations
| Hong Kong | |
| Novartis Investigative Site | |
| Hong Kong, Hong Kong | |
| Japan | |
| Novartis Investigative Site | |
| Nagoya-city, Aichi, Japan, 466-8650 | |
| Novartis Investigative Site | |
| Toyoake city, Aichi, Japan, 470 1192 | |
| Novartis Investigative Site | |
| Kashiwa, Chiba, Japan, 277 8577 | |
| Novartis Investigative Site | |
| Matsuyama-city, Ehime, Japan, 790-8524 | |
| Novartis Investigative Site | |
| Fukuoka city, Fukuoka, Japan, 812-8582 | |
| Novartis Investigative Site | |
| Fukushima city, Fukushima, Japan, 960 1295 | |
| Novartis Investigative Site | |
| Gifu shi, Gifu, Japan, 500 8513 | |
| Novartis Investigative Site | |
| Maebashi, Gunma, Japan, 371-0821 | |
| Novartis Investigative Site | |
| Sapporo, Hokkaido, Japan, 064 0804 | |
| Novartis Investigative Site | |
| Isehara, Kanagawa, Japan, 259-1193 | |
| Novartis Investigative Site | |
| Yokohama-city, Kanagawa, Japan, 241-8515 | |
| Novartis Investigative Site | |
| Kochi city, Kochi, Japan, 781 8555 | |
| Novartis Investigative Site | |
| Nagasaki-city, Nagasaki, Japan, 852-8501 | |
| Novartis Investigative Site | |
| Okayama city, Okayama, Japan, 701-1192 | |
| Novartis Investigative Site | |
| Osaka Sayama, Osaka, Japan, 589 8511 | |
| Novartis Investigative Site | |
| Osaka-city, Osaka, Japan, 543-8555 | |
| Novartis Investigative Site | |
| Hamamatsu, Shizuoka, Japan, 432-8580 | |
| Novartis Investigative Site | |
| Shimotsuke, Tochigi, Japan, 329-0498 | |
| Novartis Investigative Site | |
| Bunkyo ku, Tokyo, Japan, 113-8677 | |
| Novartis Investigative Site | |
| Bunkyo-ku, Tokyo, Japan, 113-8603 | |
| Novartis Investigative Site | |
| Shinagawa ku, Tokyo, Japan, 141 8625 | |
| Novartis Investigative Site | |
| Aomori, Japan, 030 8553 | |
| Novartis Investigative Site | |
| Fukuoka, Japan, 810-8563 | |
| Novartis Investigative Site | |
| Kyoto, Japan, 606 8507 | |
| Novartis Investigative Site | |
| Osaka, Japan, 534-0021 | |
| Novartis Investigative Site | |
| Yamagata, Japan, 990 9585 | |
| Korea, Republic of | |
| Novartis Investigative Site | |
| Seoul, Seocho Gu, Korea, Republic of, 06591 | |
| Novartis Investigative Site | |
| Seoul, Korea, Republic of, 03722 | |
| Novartis Investigative Site | |
| Seoul, Korea, Republic of, 06351 | |
| Russian Federation | |
| Novartis Investigative Site | |
| Kirov, Russian Federation, 610027 | |
| Novartis Investigative Site | |
| Moscow, Russian Federation, 123182 | |
| Novartis Investigative Site | |
| Moscow, Russian Federation, 125284 | |
| Novartis Investigative Site | |
| Samara, Russian Federation, 443079 | |
| Novartis Investigative Site | |
| St Petersburg, Russian Federation, 194044 | |
| Taiwan | |
| Novartis Investigative Site | |
| Putzu City, Chiayi Hsien, Taiwan, 61363 | |
| Novartis Investigative Site | |
| Kaohsiung City, Taiwan, 83301 | |
| Novartis Investigative Site | |
| Taipei, Taiwan, 10002 | |
| Novartis Investigative Site | |
| Taoyuan, Taiwan, 33305 | |
| Thailand | |
| Novartis Investigative Site | |
| Bangkok, Thailand, 10700 | |
| Vietnam | |
| Novartis Investigative Site | |
| Hanoi, Vietnam, 100000 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03280030 |
| Other Study ID Numbers: |
CPKC412A2220 |
| First Posted: | September 12, 2017 Key Record Dates |
| Last Update Posted: | February 24, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
|
midostaurin PKC412 cytarabine daunorubicin acute myeloid leukemia |
combination treatment FLT3 acute myeloid leukemia (AML) acute myelogenous leukemia (AML) |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms |
Midostaurin Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |