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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00782067




Registration number
NCT00782067
Ethics application status
Date submitted
28/10/2008
Date registered
29/10/2008
Date last updated
15/11/2018

Titles & IDs
Public title
Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia
Scientific 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
Secondary ID [1] 0 0
2008-000280-42
Secondary ID [2] 0 0
CPKC412D2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Midostaurin (PKC412)

Experimental: 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.


Treatment: Drugs: Midostaurin (PKC412)
Midostaurin was provided as 25 mg soft gelatin capsules for oral administration.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up 5 years
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Up 5 years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up 5 years
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up 5 years
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
Up to 30 days after last dose of study treatment
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up 5 years

Eligibility
Key inclusion criteria
Key inclusion criteria:

- 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:

- 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-a, or 2 chlorodeoxyadenosine within 30 days prior to start of midostaurin
treatment.

- Patients who had ASM with eosinophilia and known positivity for the FIP1L1- PDGFRa
fusion unless they had demonstrated relapse or disease progression on prior imatinib
therapy.

- 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Austria
State/province [9] 0 0
Wien
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
France
State/province [12] 0 0
Amiens
Country [13] 0 0
France
State/province [13] 0 0
Paris cedex 15
Country [14] 0 0
Germany
State/province [14] 0 0
Baden-Württemberg
Country [15] 0 0
Germany
State/province [15] 0 0
Nordrhein-Westfalen
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Hamburg
Country [18] 0 0
Germany
State/province [18] 0 0
Leipzig
Country [19] 0 0
Netherlands
State/province [19] 0 0
Groningen
Country [20] 0 0
Norway
State/province [20] 0 0
Oslo
Country [21] 0 0
Poland
State/province [21] 0 0
Gdansk
Country [22] 0 0
Turkey
State/province [22] 0 0
Istanbul
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow - Scotland
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Liverpool
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/show/NCT00782067
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications