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)
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Jason Robert Gotlib
- Enrollment
- 26
- Locations
- 3
- Primary Endpoint
- Subjects With Clinical Response [Partial Response (PR) + Complete Response (CR)]
Overview
Brief Summary
The safety and efficacy of midostaurin (PKC412), a novel investigational drug, will be evaluated on the basis of response rate, when administered to patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia (MCL)
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Midostaurin
100 mg midostaurin twice daily as oral capsules
Intervention: Midostaurin (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall Survival (OS)(40 months)
Investigators
Jason Robert Gotlib
Professor of Medicine
Stanford University