Conditions: Aggressive Systemic Mastocytosis Mast Cell Leukemia Systemic Mastocytosis
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 4
Healthy volunteers: no

Brief summary:
This phase 2 trial studies ibrutinib to see how well it works in treating patients with systemic (affecting the entire body) mastocytosis that has spread to other parts of the body and usually cannot be cured or controlled with treatment (advanced). Systemic mastocytosis is a disease in which too many mast cells (a type of immune system cell) are found throughout the body. Mast cells give off chemicals such as histamine that can cause flushing (a hot, red face), itching, abdominal cramps, muscle pain, nausea, vomiting, diarrhea, low blood pressure, and shock. Ibrutinib may stop the growth of mast cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVE:

Evaluate the response rate to ibrutinib in patients with advanced systemic mastocytosis (SM) (aggressive systemic mastocytosis \[ASM\] or mast cell leukemia \[MCL\], or SM-associated hematologic non-mast cell disorder \[AHNMD\]) by the end of 6 cycles (6 months).

SECONDARY OBJECTIVES:

* Evaluate the tolerability and safety profile of ibrutinib in patients with advanced SM.
* Evaluate the pharmacokinetic (PK) profile of ibrutinib in a subset of patients with advanced SM.
* Evaluate changes in histopathology (blood and bone marrow) of patients with advanced SM in response to ibrutinib therapy.
* Evaluate changes in mastocytosis related symptom scores and quality-of-life (QOL) using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).
* Evaluate the duration of response (DoR) and time to response (TTR).
* Evaluate progression-free survival (PFS) and overall survival.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1 to 28. Treatment repeats every 28 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving an unconfirmed or confirmed clinical improvement (CI), partial response (PR), or complete response (CR) by the end of course 6 will be permitted to continue maintenance courses of ibrutinib on an ongoing basis until loss of response/progressive disease, or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 6 months thereafter.

Arms:
arm 1: Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles arm 2: Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles

Interventions: intervention 1: Ibrutinib
Intervention descriptions: intervention 1: Given orally in 28-day cycles

Protocol document: