LeukemiaPhase 2NCT00782067
Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia
A Phase 2 study testing Midostaurin (PKC412) in people with Leukemia, run by Novartis Pharmaceuticals at 29 sites in 12 countries.
Trial summary
The purpose of this study was to determine the efficacy and safety of twice daily (bid) oral midostaurin in patients with Aggressive Systemic Mastocytosis (ASM) or Mast Cell Leukemia (MCL) with or without an Associated Hematological clonal Non-Mast cell lineage Disease (AHNMD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- Midostaurin (PKC412)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 29 sitesin 12 countries
- Study dates
- 13 Oct 2008to 24 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years of age who provided written informed consent, Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 and a life expectancy of >12 weeks, electrocardiogram with a QTcF of ≤ 450 ms, with a diagnosis of SM and sub-variants based on WHO criteria.
- Patients with ASM or MCL were to have one or more measurable clinical findings (termed "C-findings") and defined as those attributable to the mast cell disease component and not to AHNMD or any other cause.
- Patients with MCL were to have BM aspirate smears with ≥ 20% immature MCs. Patients with AHNMD were eligible if it was not life-threatening or in an acute stage.
Who cannot join
- Patients with cardiovascular disease including congestive heart failure class III or IV according to the New York Heart Association classification, left ventricular ejection fraction (LVEF) of <50%, myocardial infarction within the previous 6 months, or poorly controlled hypertension.
- Patients with a heart block of any degree at screening (for Canada only).
- Patients with an AHNMD who required immediate cytoreductive therapy or targeted therapy (other than midostaurin).
- Patients who had demonstrated relapse after 3 or more prior regimens of SM treatment regardless of treatment regimen for supportive care (e.g., symptom-limiting therapies).
- Patients who had received any investigational agent, targeted therapy, chemotherapy, interferon-α, or 2 chlorodeoxyadenosine within 30 days prior to start of midostaurin treatment.
- Patients who had ASM with eosinophilia and known positivity for the FIP1L1- PDGFRα fusion unless they had demonstrated relapse or disease progression on prior imatinib therapy.
Show all 10Show fewer
- Patients who had received any treatment with midostaurin prior to study entry.
- Patients who had received hematopoietic growth factor support within 14 days of Day 1 of midostaurin treatment.
- Patients who had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1 of midostaurin treatment.
- Patients with any pulmonary infiltrate, including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray were not eligible until the pulmonary infiltrates had completely resolved. Exception: patients with ASM/MCL ± AHNMD-related pleural effusion as judged by the Investigator and approved by the SSC Chairperson or designee were permitted to enter the study.
Trial locations and contacts
29 sites in 12 countries.
29 sites in 12 countries
United States9 sites
University of Michigan Comprehensive Cancer Center DeptofMichiganCancerCenter(3)
Ann Arbor, Michigan, +1 48109 0944
Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
Augusta, Georgia, 30912
Dana Farber Cancer Institute Hematology / Oncology
Boston, Massachusetts, 02215
University of California at Los Angeles Dept. of Hematology Clinic
Los Angeles, California, 90095
Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)
New York, New York, 10021
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University Dept. Hematologic Malignancies
Portland, Oregon, 97239
Virginia Commonwealth University SC
Richmond, Virginia, 23284
Stanford University Medical Center Stanford University 2
Stanford, California, 94305-5750
Germany5 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68305
United Kingdom3 sites
Novartis Investigative Site
Glasgow - Scotland, G12 OYN
Novartis Investigative Site
Liverpool, L7 8XP
Novartis Investigative Site
London, SE1 7EH
Australia2 sites
Novartis Investigative Site
Camperdown, New South Wales, 2050
Novartis Investigative Site
Prahran, Victoria, 3181
Canada2 sites
Novartis Investigative Site
London, Ontario, N6A 4G4
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
France2 sites
Novartis Investigative Site
Amiens, 80054
Novartis Investigative Site
Paris, 75015
About this study
Official title: A Single Arm, Phase II, Open-Label Study to Determine the Efficacy of 100mg Twice Daily Oral Dosing of Midostaurin Administered to Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia +/- an Associated Hematological Clonal Non-Mast Cell Lineage Disease
The purpose of this study was to determine the efficacy and safety of twice daily (bid) oral midostaurin in patients with Aggressive Systemic Mastocytosis (ASM) or Mast Cell Leukemia (MCL) with or without an Associated Hematological clonal Non-Mast cell lineage Disease (AHNMD).
- Conditions
- Leukemia
- Being tested
- Midostaurin (PKC412)
- Keywords
- Aggressive systemic mastocytosis, mast cell leukemia, C-Findings, tyrosine kinase inhibitor, KIT mutation, AHNMD, Systemic, Aggressive
- Medical subject headings
- Leukemia, Mastocytosis, Systemic, Leukemia, Mast-Cell, Aggression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midostaurin (PKC412)Drug
Midostaurin was provided as 25 mg soft gelatin capsules for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Midostaurin (PKC412) | Experimental | Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first. Receives: Drug: Midostaurin (PKC412) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the percentage of participants who classified as confirmed responders (Major Response (MR) or Partial Response (PR)) by the adjudication of the SSC and based on a Modified Valent Criteria.
A major responder had complete resolution of at least one C-Finding and no progression in other C-Findings. A partial responder showed a measurable improvement in one or more C-Finding(s) without confirmed progression in other C-Findings. A C-Finding was a Clinical Finding, which was considered by the investigator and corroborated by the Study Steering Committee (SSC) Chairperson or designee, attributable to the mast cell disease component and not the associated hematological clonal non-mast cell lineage disease (AHNMD) component or any other cause.
Measured: 6 months
Secondary outcomes (6)
Median Time to Duration of Response (DoR)
The Duration of response (DoR) was defined as the time from first onset of confirmed response (MR or PR) to the date of first documented and confirmed progression or death due to ASM/MCL.
Measured: Up 5 years
Median Time to Response (TTR)
The Time to response (TTR) was defined as the time from start of treatment until the date of onset of confirmed response (MR or PR).
Measured: Up 5 years
Median Time to Progression-Free Survival (PFS)
The Progression-free survival (PFS) is defined as the time from start of treatment to the date of the first documented and confirmed progression or death due to any cause.
Measured: Up 5 years
Median Time to Overall Survival (OS)
The Overall Survival (OS) is defined as the time from start of treatment to the date of death due to any cause.
Measured: Up 5 years
Long-term Safety and Tolerability of Midostaurin
Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)
Measured: Up to 30 days after last dose of study treatment
Histopathologic Response
Histopathologic response was summarized to demonstrate the change from baseline in percentage of mast cell infiltrations in the Bone Marrow (BM) and related serum tryptase levels.
Measured: Up 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2008 (estimated)
- Study start13 Oct 2008
- Primary completion1 Dec 2014
- Study completion24 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00782067
- Sponsor's protocol ID
- CPKC412D2201
- Other IDs
- 2008-000280-42, 2008
- Status last verified
- Oct 2018
- First submitted
- 28 Oct 2008
- Last updated
- 15 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Publications
Medawar G, Sakalabaktula K, Magri J, Rinker E, Baratam P. KIT V560D-Mutated Systemic Mastocytosis Associated With High-Risk Myelodysplastic Syndrome: A Unique Case of Systemic Mastocytosis-Associated Hematologic Neoplasm. Case Rep Hematol. 2024 Nov 30;2024:4360304. doi: 10.1155/crh/4360304. eCollection 2024.
PubMed 39649724Hartmann K, Gotlib J, Akin C, Hermine O, Awan FT, Hexner E, Mauro MJ, Menssen HD, Redhu S, Knoll S, Sotlar K, George TI, Horny HP, Valent P, Reiter A, Kluin-Nelemans HC. Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis. J Allergy Clin Immunol. 2020 Aug;146(2):356-366.e4. doi: 10.1016/j.jaci.2020.03.044. Epub 2020 May 11.
PubMed 32437738Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. doi: 10.1056/NEJMoa1513098.
PubMed 27355533
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Phase II, Open-Label Study to Determine the Efficacy of 100mg Twice Daily Oral Dosing of Midostaurin Administered to Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia +/- an Associated Hematological Clonal Non-Mast Cell Lineage Disease
- ClinicalTrials.gov ID
- NCT00782067
- Acronym / sponsor ID
- CPKC412D2201
- Conditions
- Leukemia
- Keywords
- Aggressive systemic mastocytosis, mast cell leukemia, C-Findings, tyrosine kinase inhibitor, KIT mutation, AHNMD, Systemic, Aggressive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Oct 2008 (actual)
- Primary completion
- 1 Dec 2014 (actual)
- Study completion
- 24 Aug 2017 (actual)
- First posted
- 29 Oct 2008 (estimated)
- Results
- Posted 6 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine the efficacy and safety of twice daily (bid) oral midostaurin in patients with Aggressive Systemic Mastocytosis (ASM) or Mast Cell Leukemia (MCL) with or without an Associated Hematological clonal Non-Mast cell lineage Disease (AHNMD).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Midostaurin (PKC412) | Experimental | Drug: Midostaurin (PKC412)Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients ≥ 18 years of age who provided written informed consent, Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 and a life expectancy of >12 weeks, electrocardiogram with a QTcF of ≤ 450 ms, with a diagnosis of SM and sub-variants based on WHO criteria.
- Patients with ASM or MCL were to have one or more measurable clinical findings (termed "C-findings") and defined as those attributable to the mast cell disease component and not to AHNMD or any other cause.
- Patients with MCL were to have BM aspirate smears with ≥ 20% immature MCs. Patients with AHNMD were eligible if it was not life-threatening or in an acute stage.
Key exclusion criteria (10 listed)
- Patients with cardiovascular disease including congestive heart failure class III or IV according to the New York Heart Association classification, left ventricular ejection fraction (LVEF) of <50%, myocardial infarction within the previous 6 months, or poorly controlled hypertension.
- Patients with a heart block of any degree at screening (for Canada only).
- Patients with an AHNMD who required immediate cytoreductive therapy or targeted therapy (other than midostaurin).
- Patients who had demonstrated relapse after 3 or more prior regimens of SM treatment regardless of treatment regimen for supportive care (e.g., symptom-limiting therapies).
- Patients who had received any investigational agent, targeted therapy, chemotherapy, interferon-α, or 2 chlorodeoxyadenosine within 30 days prior to start of midostaurin treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Midostaurin (PKC412)Midostaurin was provided as 25 mg soft gelatin capsules for oral administration. | Drug | Midostaurin (PKC412) |
Primary outcome
Percentage of Participants With Overall Response Rate (ORR)
Time frame: 6 months
Overall Response Rate (ORR) was defined as the percentage of participants who classified as confirmed responders (Major Response (MR) or Partial Response (PR)) by the adjudication of the SSC and based on a Modified Valent Criteria. A major responder had complete resolution of at least one C-Finding and no progression in other C-Findings. A partial responder showed a measurable improvement in one or more C-Finding(s) without confirmed progression in other C-Findings. A C-Finding was a Clinical Finding, which was considered by the investigator and corroborated by the Study Steering Committee (SSC) Chairperson or designee, attributable to the mast cell disease component and not the associated hematological clonal non-mast cell lineage disease (AHNMD) component or any other cause.
6 secondary outcomes
Median Time to Duration of Response (DoR)
Time frame: Up 5 years
Median Time to Response (TTR)
Time frame: Up 5 years
Median Time to Progression-Free Survival (PFS)
Time frame: Up 5 years
Median Time to Overall Survival (OS)
Time frame: Up 5 years
Long-term Safety and Tolerability of Midostaurin
Time frame: Up to 30 days after last dose of study treatment
Histopathologic Response
Time frame: Up 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39649724Medawar G, Sakalabaktula K, Magri J, Rinker E, Baratam P. KIT V560D-Mutated Systemic Mastocytosis Associated With High-Risk Myelodysplastic Syndrome: A Unique Case of Systemic Mastocytosis-Associated Hematologic Neoplasm. Case Rep Hematol. 2024 Nov 30;2024:4360304. doi: 10.1155/crh/4360304. eCollection 2024.
- Derived from this study: PubMed 32437738Hartmann K, Gotlib J, Akin C, Hermine O, Awan FT, Hexner E, Mauro MJ, Menssen HD, Redhu S, Knoll S, Sotlar K, George TI, Horny HP, Valent P, Reiter A, Kluin-Nelemans HC. Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis. J Allergy Clin Immunol. 2020 Aug;146(2):356-366.e4. doi: 10.1016/j.jaci.2020.03.044. Epub 2020 May 11.
- Derived from this study: PubMed 27355533Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, Awan FT, Hexner E, Mauro MJ, Sternberg DW, Villeneuve M, Huntsman Labed A, Stanek EJ, Hartmann K, Horny HP, Valent P, Reiter A. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016 Jun 30;374(26):2530-41. doi: 10.1056/NEJMoa1513098.
- Individual participant dataSharing planned: Undecided. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
29 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midostaurin (PKC412) in people with Leukemia, run by Novartis Pharmaceuticals at 29 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Germany, United Kingdom, Australia, Canada and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Overall Response Rate (ORR) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00782067, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2018.