Ontak (Denileukin Diftitox) in Patients With Systemic Mastocytosis (SM)
Ontak (Denileukin Diftitox) in Patients With Systemic Mastocytosis (SM)
Primary Objective:

 1. To assess the response rate of ONTAK in Systemic Mastocytosis (SM) patients.

 Secondary Objectives:

 1. To assess the safety of ONTAK in SM patients.

 2. To evaluate the time to progression and duration of response following treatment with
 ONTAK.
Denileukin diftitox has been used for the treatment of a variety of disorders, in particular,
 malignant lymphoma, another blood-related disease. Denileukin diftitox is believed to be able
 to specifically attach to and kill malignant mast cells.

 Before you can start treatment on this study, you will have what are called "screening
 tests". These tests will help the doctor decide if you are eligible to take part in the
 study. You will have blood (around 2 teaspoons) and bone marrow samples collected. To collect
 a bone marrow sample, an area of the hip bone is numbed with anesthetic and a small amount of
 bone marrow is withdrawn through a large needle. These samples will be used for tests to
 confirm the diagnosis of the disease. Women who are able to have children must have a
 negative blood pregnancy test.

 If you are found to be eligible, you will receive denileukin diftitox as an injection by vein
 once a day for 5 days in a row. This will be repeated every 3 weeks (1 cycle). You will
 receive treatment on an outpatient basis. Treatment will continue as long as there is
 evidence that therapy is affecting the disease and is beneficial to you. If the disease gets
 worse or you experience any intolerable side effects, you will be taken off the study and
 your doctor will discuss other treatment options with you.

 During treatment you will have blood (around 1 teaspoon) collected twice during every 3-week
 period. You will also have bone marrow samples collected every 3 months during the treatment.

 After the end of treatment, blood and bone marrow samples will be collected every 3 months
 until the disease gets worse or you start a different therapy. The blood and bone marrow
 samples will be used to look at response to therapy.

 This is an investigational study. Denileukin diftitox has been approved by the FDA for the
 treatment of skin T-cell lymphoma and is commercially available. The use of denileukin
 diftitox in this study is investigational. You will be provided denileukin diftitox free of
 charge. Up to 25 participants will take part in this study. All be enrolled at M. D.
 Anderson.
Inclusion Criteria:

 -  Patients with SM, including mast cell leukemia (MCL).

 -  ECOG Performance Status (PS) 0-3

 -  Adequate renal function (indicated by serum creatinine </= 2.5 mg/dL); adequate
 hepatic function (indicated by ALT </= 3 * upper limit of normal; total bilirubin </=
 3 * upper limit of normal; and albumin >/= 2.8 g/dL).

 -  Provide written informed consent.

 -  Female patients of childbearing potential must have a negative pregnancy test within
 14 days prior to first dose of study drug, and must agree to use an effective means of
 contraception following the pregnancy test, throughout the study and for at least
 three weeks after their last treatment on protocol.

 Exclusion Criteria:

 -  History of hypersensitivity to diphtheria toxin.

 -  Active cardiovascular disease as defined by New York Heart Association (NYHA) Class
 III-IV categorization.

 -  Serious intercurrent medical illnesses or active infections requiring parenteral
 antibiotics that would interfere with the ability of the patient to carry out the
 treatment program.

 -  Concurrent malignancy (other than resected basal or squamous cell skin cancers or
 in-situ cervical cancer). Unless, patient has SM-associated clonal hematologic disease
 that does not require therapy, as judged by treating physician and approved by
 principal investigator.

 -  Female patients who are pregnant or breastfeeding.

 -  No chemotherapy, radiotherapy, immunotherapy, hormonal anticancer therapy, or
 experimental medications (including approved drugs tested in an investigational
 setting) may be administered while a patient is a participant in this protocol.