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A Single Arm, Phase II, Open-Label Study to Determine the Efficacy of Twice Daily Oral Dosing of PKC412 Administered to Patients With Aggressive Systemic Mastocytosis (ASM) and Mast Cell Leukemia (MCL)

Phase 2
18 Years
Open (Enrolling)
Mastocytosis, Systemic, Leukemia, Mast-Cell

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Trial Information

A Single Arm, Phase II, Open-Label Study to Determine the Efficacy of Twice Daily Oral Dosing of PKC412 Administered to Patients With Aggressive Systemic Mastocytosis (ASM) and Mast Cell Leukemia (MCL)

To evaluate the activity and safety profile of a novel investigational drug, PKC412, in
patients with ASM/MCL. Aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL)
are characterized by excessive bone marrow production of mast cells which can release
harmful substances, and can infiltrate tissues, resulting in organ damage. These diseases
have very limited treatment options and poor prognosis. Existing treatments such as
interferon-alpha +/-, corticosteroids, and cladribine exhibit low response rates in advanced
mast cell disease and are usually partial in nature.

Inclusion Criteria:

- Histologically documented aggressive systemic mastocytosis or mast cell leukemia +
AHNMD, regardless of the presence of absence of the D816V c-kit mutation, or the
FIP1L1-PDGFR alpha fusion.

- Tissue for evaluation of KIT mutation status of the tumor cells must be collected and
availability confirmed by PI within 6 months prior to entry into study (e.g.
wild-type, D816V, or other KIT mutation). Patients who have systemic mastocytosis
with eosinophilia and known positivity for the FIP1L1-PDGFR alpha fusion are also
eligible only if they have demonstrated relapse or disease progression on prior
imatinib therapy.

- Karnofsky performance status of >30%.

- Liver enzyme values within normal limits unless the sole cause of liver elevation is
due to ASM/MCL. Else, patients must have the following laboratory values: AST and
ALT <= 4X ULN, and/or bilirubin <= 4X ULN if elevation of liver enzymes is considered
solely due to ASM/MCL.

- Serum creatinine <2.0 mg/dL

- For patients with grade >2 blood values, the screening bone marrow exam (e.g.
presence of mast cell infiltrate as defined in Appendix B) and/or the presence of
disease-related hypersplenism should establish that the likely causes of these
cytopenia(s) is related to ASM/MCL.

- No clinical or radiographic (by PA and lateral chest x-ray) evidence of active
pulmonary disease which is considered by the investigator to be unrelated to

- Patient must give written informed consent.

Exclusion Criteria:

- Female patients who are pregnant or breast-feeding, or any adult, male or female, of
reproductive potential not agreeing to employ barrier contraceptives throughout the

- Women of childbearing potential must have a negative serum pregnancy test 48 hours
prior to administration of study drug, are required to use barrier contraception for
the duration of the study and for 3 months post study because of the long half life
of the metabolite, CGP52421, and must avoid breast-feeding.

- Any other known disease, concurrent severe and/or uncontrolled medical condition
(e.g. uncontrolled diabetes, cardiovascular disease including congestive heart
failure, myocardial infarction within 6 months, any Grade 3/4 cardiac problems as
defined by the New York Heart Association Criteria and poorly controlled
hypertension, chronic renal disease, active uncontrolled infection) which could
compromise participation in the study.

- Known confirmed diagnosis of HIV infection or active viral hepatitis.

- Patients who have received any investigational agent, chemotherapy, or
2-chlorodeoxyadenosine (2-CdA) within 30 days prior to Day 1 of PKC412 treatment.

- Patients who have received interferon-alpha within 30 days prior to Day 1 of PKC412

- Patients who have received hematopoietic growth factor support within 14 days of Day
1 of PKC412 treatment.

- Glucocorticoids should be tapered off within 14 days of Day 1 of PKC412 treatment if
it is anticipated that patients can be tapered off these drugs. Otherwise, for
glucocorticoid-requiring patients, investigators should attempt to taper to the
minimal dose possible at the time of PKC412 start on day 1.

- Patients who have had any surgical procedure, excluding central venous catheter
placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1 of
PKC412 treatment.

- Patients unwilling or unable to comply with the protocol.

- Patients with known malignant disease involving the central nervous system.

- Patient with any pulmonary infiltrate or abnormality on the baseline chest X-ray
known to be new in the previous 4 weeks. However, if a patient has a pleural
effusion which is considered related to systemic mastocytosis (e.g. secondary to
ascites) and not causing symptomatic respiratory complaints, the patient may be
eligible after discussion with the sponsor.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the efficacy of twice-daily oral doses of PKC412 when administered to patients with ASM/MCL + AHNMD (associated hematological clonal non-mast cell lineage disease) by measuring response rate.

Outcome Time Frame:


Safety Issue:


Principal Investigator

Jason Robert Gotlib

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Institutional Review Board

Study ID:




Start Date:

March 2005

Completion Date:

November 2011

Related Keywords:

  • Mastocytosis, Systemic
  • Leukemia, Mast-Cell
  • Leukemia
  • Leukemia, Mast-Cell
  • Mastocytosis
  • Urticaria Pigmentosa
  • Mastocytoma
  • Mastocytosis, Systemic



Stanford University School of Medicine Stanford, California  94305-5317
Dana Farber Cancer Institute Boston, Massachusetts  02115
Washington University-St. Louis St. Louis, Missouri  63110