Phase 2 Midostaurin in Aggressive Systemic Mastocytosis and Mast Cell Leukemia
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|ClinicalTrials.gov Identifier: NCT00233454|
Recruitment Status : Completed
First Posted : October 5, 2005
Results First Posted : July 9, 2015
Last Update Posted : September 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Systemic Mastocytosis, Aggressive (ASM) Leukemia, Mast Cell Hematological Non-mast Cell Lineage Disease (AHNMD)||Drug: Midostaurin||Phase 2|
This study assesses the activity and safety profile of twice-daily oral doses of midostaurin in patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL) with or without associated clonal hematological non-mast cell lineage disease (AHNMD).
Aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) are characterized by excessive bone marrow production of mast cells which can can infiltrate tissues and release harmful substances, resulting in organ damage. These diseases have very limited treatment options and poor prognosis. Existing treatments for in advanced mast cell disease, eg, interferon-alpha; corticosteroids; and/or cladribine, exhibit low response rates that are usually partial in nature.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single Arm, Phase 2, Open-Label Study to Determine the Efficacy of Twice Daily Oral Dosing of PKC412 <Midostaurin> Administered to Patients With Aggressive Systemic Mastocytosis (ASM) and Mast Cell Leukemia (MCL)|
|Actual Study Start Date :||March 2005|
|Actual Primary Completion Date :||June 18, 2010|
|Actual Study Completion Date :||April 16, 2011|
100 mg midostaurin twice daily as oral capsules
Midostaurin is a broad-spectrum protein kinase inhibitor, acting on conventional PKC isoforms (α, β, γ); PDFRβ; VEGFR2; Syk; PKCη; Flk-1; Flt3; Cdk1/B; PKA; c-Kit; c-Fgr; c-Src; VEGFR1; and EGFR
- Subjects With Clinical Response [Partial Response (PR) + Complete Response (CR)] [ Time Frame: 2 months ]
Clinical Response [PR + CR] will be assessed after 2 cycles of treatment, with each cycle being 28 days (4 weeks) in length.
Except as otherwise noted, the minimum criteria for PR is improvement by at least 50% from the baseline value towards the indicated value for one or more of the criteria below:
BONE MARROW & BLOOD
- ANC <1000/uL
- Hb <10 g/dL
- Platelets >100,000/uL LIVER
- If hepatomegaly with ascites, decrease in frequency of paracenteses by 50%
- Elevated enzyme levels > upper limit of normal (ULN)
- Hypoalbuminemia < ULN
- Portal hypertension > ULN SPLEEN
- If palpable splenomegaly with hypersplenism/thrombocytopenia, hypersplenism markers improved GI TRACT
- If malabsorption with hypoalbuminemia and/or weight loss, albumin improved BONES
- If huge osteolyses or/and severe osteoporosis with pathologic fractures, partial resolution of osteolyses
Subjects with PR or greater continue, those without response discontinue.
- Overall Survival (OS) [ Time Frame: 11 months ]Overall survival will be assessed after 12 cycles of treatment, with each cycle being 28 days (4 weeks) in length. 12 cycles of treatment is considered to be about 11 months.
- Overall Survival (OS) [ Time Frame: 40 months ]Overall survival was assessed as the median duration of survival at the time of data cut-off, and reported with 95% confidence interval.
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): NCT00233454
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Missouri|
|Washington University-St. Louis|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Jason Robert Gotlib||Stanford University|