Phase 2 Midostaurin in Aggressive Systemic Mastocytosis and Mast Cell Leukemia

Jason Robert Gotlib

Status and phase

Completed

Phase 2

Conditions

Leukemia, Mast Cell

Systemic Mastocytosis, Aggressive (ASM)

Hematological Non-mast Cell Lineage Disease (AHNMD)

Treatments

Drug: Midostaurin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00233454

95242 (Other Identifier)

HEMMPD0003 (Other Identifier)

2213 (Other Identifier)

IRB-13704

CPKC412D2201 (Other Identifier)

Details and patient eligibility

About

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)

Full 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.

Enrollment

26 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

At least 18 years of age.
Karnofsky performance status (KPS) of > 30% (equivalent to ECOG 0 to 3)
Mast cell disease, histologically confirmed and documented to be
- Aggressive systemic mastocytosis (ASM) OR
- Mast cell leukemia (MCL) meeting the following criteria
  - Meets criteria for systemic mastocytosis
  - Biopsy indicates diffuse infiltration by atypical, immature mast cells
  - Bone marrow aspirate smears show at least 20% mast cells
Confirmed availability of tissue sample within 6 months prior to entry into study, for evaluation of KIT mutation status of the tumor cells. Subjects who have systemic mastocytosis PLUS eosinophilia AND known positivity for FIP1L1-PDGFR-alpha fusion are eligible only if they have demonstrated relapse or disease progression on prior imatinib therapy
Blood levels of liver enzymes within normal limits (EXCEPTION: If the sole cause of elevated blood levels of liver enzymes is ASM/MCL, then AST and ALT ≤ 4X upper limit of normal (ULN), and/or bilirubin ≤ 4X ULN)
Serum creatinine < 2.0 mg/dL
If ANC < 1500/mm3; Hb < 10 g/dL; platelets < 75,000/mm3; AND/OR other blood values are > grade 2, then the relationship of these cytopenia(s) should be established as related to ASM or MCL on the basis of presence of mast cell infiltrate in the screening bone marrow exam and/or the presence of disease-related hypersplenism
Prior use of glucocorticoids must be tapered off within 14 days of Day 1 of midostaurin treatment (EXCEPTION: If in the opinion of the investigator, the subject can be tapered off glucocorticoids, then dosage should be tapered to the minimal dose possible before first treatment with midostaurin)
Negative serum pregnancy test for women of childbearing potential within 48 hours prior to administration of study drug
Written informed consent.
Anyone of reproductive potential must agree to use barrier contraceptives for the duration of the study
Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of study drug, and must agree to:
- Use barrier contraception for the duration of the study
- Use barrier contraception for 3 months post-study
- Not breast-feed

Exclusion criteria

Active pulmonary disease based on physical assessment or lateral chest X-ray, considered by the investigator to be unrelated to mastocytosis
Any pulmonary infiltrate or abnormality on the baseline chest X-ray known to be new in the previous 4 weeks (EXCEPTION: pleural effusion related to systemic mastocytosis, eg, secondary to ascites, AND not causing symptomatic respiratory complaints, may be eligible)
Cardiovascular disease, including congestive heart failure
Myocardial infarction within 6 months
Poorly-controlled hypertension with any Grade 3/4 cardiac problems (per New York Heart Association Criteria)
Uncontrolled diabetes
Chronic renal disease
Active uncontrolled infection
Known malignant disease involving the central nervous system (CNS)
Known confirmed diagnosis of HIV infection or active viral hepatitis.
Any other known disease, or concurrent severe and/or uncontrolled medical condition which could compromise participation in the study, including but not limited to:
Received any investigational agent, chemotherapy, or 2-chlorodeoxyadenosine (2-CdA) within 30 days prior to Day 1 of PKC412 treatment.
Received interferon-alpha within 30 days prior to Day 1 of midostaurin treatment.
Received hematopoietic growth factor support within 14 days of Day 1 of midostaurin treatment.
Any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of Day 1 of midostaurin treatment
Pregnant or breast-feeding
Unwilling or unable to comply with the protocol