A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis with Symptoms Inadequately Controlled with Standard Therapy

Phase 2

Recruiting

• Conditions: mastcell disease; 10018849

• Registration Number: NL-OMON52372
• Lead Sponsor: Blueprint Medicines Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 12

Inclusion Criteria

1. Patient must be >= 18 years of age.
2. Patient must have SM, confirmed by Central Pathology Review of BM biopsy,
and central review of B- and C-findings by WHO diagnostic criteria.
3. Patient must have moderate-to-severe symptoms based on minimum mean TSS over
the
14-day eligibility screening period for assessment of TSS and. Minimum TSS for
eligibility is >= 28.
4. Patient must have failed to achieve adequate symptom control for 1 or more
baseline symptoms
, as determined by the Investigator, with at least 2 of the following
symptomatic therapies: H1 blockers, H2 blockers, Proton-pump inhibitors,
Leukotriene inhibitors, Cromolyn sodium, Corticosteroids, Omalizumab.
5. The patient*s symptomatic SM therapies (eg, H1 and H2 blockers) must be
stable (same dose, no new medications >= 14 days before beginning the 14-day
ISM-SAF eligibility TSS assessment).
6. For patients receiving corticosteroids, the dose must be <= 20 mg/d
prednisone or equivalent, and the dose must be stable for >= 14 days before
beginning the 14-day ISM-SAF eligibility TSS assessment.
7. Patient must have an ECOG-PS of 0 to 2.
8. Patient must be able to give written informed consent.

Exclusion Criteria

1. Patient has been diagnosed with any of the following WHO SM
subclassifications:
o Cutaneous mastocytosis only (ie, without documentation of systemic
involvement).
o SM-AHN.
o SSM
o ASM.
o MCL.
o MC sarcoma.
2. Patient has been diagnosed with another myeloproliferative disorder (eg,
myelodysplastic syndrome, myeloproliferative neoplasm).
3. Patient has any of the following organ damage C-findings attributable to SM:
o Cytopenia.
o Hepatomegaly with ascites and impaired liver function.
o Palpable splenomegaly with hypersplenism.
o Malabsorption with hypoalbuminemia and significant weight loss.
o Skeletal lesions: large osteolytic lesions with pathologic fractures.
o Life-threatening organ damage in other organ systems that is caused by MC
infiltration in tissues.
4. Patient meets any of the following laboratory criteria:
o Aspartate aminotransferase or alanine aminotransferase > 3.0 × upper limit of
normal (ULN).
o Total bilirubin > 1.5 × ULN; > 3.0 × ULN if due to Gilbert's disease. (In the
case of Gilbert*s disease, a direct bilirubin > 2.0 × ULN is an exclusion.)
o Albumin < 1 × LLN.
o Estimated glomerular filtration rate (eGFR; calculated using the Modification
of Diet in Renal Disease equation) < 30 mL/min/1.73 m2 or creatinine > 1.5 ×
ULN
o Absolute neutrophil count < 1.5 × 109/L.
o Hemoglobin < 10 g/dL.
o Platelet count < 100 × 109/L.
5. Patient has received any of the following medications, therapies, or
procedures in the timeframes listed:
o Any prior treatment with avapritinib.
o Any TKI, including but not limited to masitinib and midostaurin, or
investigational agentfor < 14 days or 5 half-lives of the drug (whichever is
longer) before beginning the 14-day ISM-SAF eligibility TSS assessment
o Any antineoplastic drug therapy (including but not limited to cladribine and
interferon alpha, pegylated interferon, or antibody therapy) < 28 days or 5
half-lives of the drug (whichever is longer) before beginning the 14-day
ISM-SAF eligibility TSS assessment.
o Radiotherapy or PUVA therapy < 14 days before beginning the 14-
day ISM-SAF eligibility TSS assessment.
o Any hematopoietic growth factor the preceding 14 days before beginning the 14-
day ISM-SAF eligibility TSS assessment.
o Any major surgical procedure (minor surgical procedures such as central
venous catheter placement, BM biopsy, and feeding tube placement are not
considered major surgical procedures) < 14 days before starting the ISM-SAF for
determination of eligibility.
6. Patient requires therapy with a concomitant medication that is a strong
inhibitor, strong inducer, or moderate inducer of cytochrome P450 3A4 (CYP3A4)
(see Appendix 9).
7. Patient has a history of a malignancy that has been diagnosed or required
therapy within 3 years before the first dose of study drug. Patients with a
prior or concurrent malignancy whose natural history or treatment does not have
the potential to interfere with the safety or efficacy assessment of the
investigational agent may be included after approval by medical monitor.
8. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480
msec.
9. Patient has a history of a seizure disorder (eg, epilepsy) or requires
antiseizure medication.
10. Patient has a history of a cerebrovascular accident or transient ische

Study & Design

• Study Type: Interventional
• Study Design: Not specified