Authorised Therapeutic exploratory (Phase II) Indolent Systemic Mastocytosis (ISM)

A Study of Avapritinib in Patients with Indolent and Systemic Mastocytosis

EU CTIS ID: 2024-512585-34-00

What this study is testing

Part 1- To determine the RP2D of avapritinib in patients with ISM for use in Part 2 and Part 3 of the study. Part 2- To determine mean change in ISM-SAF TSS from baseline to C7D1, compared to placebo. Part 3- To assess the long-term safety and efficacy of avapritinib in ISM patients.

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Patients 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. 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, or omalizumab.
5. The patient's symptomatic SM therapies (e.g., 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. If the patient is receiving corticosteroids, the dose must be ≤20 mg/day prednisone or equivalent, and the dose must be stable for ≥14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.

You likely can't join if

1. Patient has been diagnosed with any of the following WHO SM subclassifications: Cutaneous mastocytosis only, SM-AHN, SSM, ASM, MCL, MC sarcoma.
10. Patient has a history of a cerebrovascular accident or transient ischemic attacks within 12 months before the first dose of study drug.
11. Patient has a known risk or recent history (12 months before the first dose of study drug) of ICB (eg, brain aneurysm).
12. Patient has a primary brain malignancy or metastases to the brain.
13. Patient has clinically significant, uncontrolled cardiovascular disease, including Grade III or Grade IV congestive heart failure greater than New York Heart Association classification II; myocardial infarction or unstable angina within the previous 6 months; clinically significant, uncontrolled arrhythmias, or uncontrolled hypertension.
14. Female patients who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the study drug administration period and for at least 6 weeks after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the study drug administration period and for at least 6 weeks after the last dose of study drug.

See the full eligibility criteria

Who can join

1. Patients 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. 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, or omalizumab.
5. The patient's symptomatic SM therapies (e.g., 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. If the patient is receiving corticosteroids, the dose must be ≤20 mg/day 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.

What rules you out

1. Patient has been diagnosed with any of the following WHO SM subclassifications: Cutaneous mastocytosis only, SM-AHN, SSM, ASM, MCL, MC sarcoma.
10. Patient has a history of a cerebrovascular accident or transient ischemic attacks within 12 months before the first dose of study drug.
11. Patient has a known risk or recent history (12 months before the first dose of study drug) of ICB (eg, brain aneurysm).
12. Patient has a primary brain malignancy or metastases to the brain.
13. Patient has clinically significant, uncontrolled cardiovascular disease, including Grade III or Grade IV congestive heart failure greater than New York Heart Association classification II; myocardial infarction or unstable angina within the previous 6 months; clinically significant, uncontrolled arrhythmias, or uncontrolled hypertension.
14. Female patients who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the study drug administration period and for at least 6 weeks after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the study drug administration period and for at least 6 weeks after the last dose of study drug.
15. Pregnant women, as documented by a β-hCG pregnancy test consistent with pregnancy obtained within 7 days before the first dose of study drug.
16. Women who are breastfeeding.
2. Patient has been diagnosed with another myeloproliferative disorder.
3. Patient has any of the following organ damage C-findings attributable to SM: Cytopenia, Hepatomegaly with ascites and impaired liver function, Palpable splenomegaly with hypersplenism, Malabsorption with hypoalbuminemia and significant weight loss, Skeletal lesions: large osteolytic lesions with pathologic fractures, 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: Aspartate aminotransferase or alanine aminotransferase > 3.0 × ULN, 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.) Albumin < 1 × LLN, eGFR < 30 mL/min/1.73 m^2 or creatinine clearance or creatinine > 1.5 × ULN Absolute neutrophil count < 1.5 × 10^9/L, Hemoglobin < 10 g/dL, Platelet count < 100,000/μL
5. Patient has received any of the following medications, therapies, or procedures in the timeframes listed: Any prior treatment with avapritinib, Any TKI, including but not limited to masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of the drug (whichever is longer) before beginning the 14-day ISM-SAF eligibility TSS assessment, Any antineoplastic drug therapy < 28 days or 5 half-lives of the drug (whichever is longer) before beginning the 14- day ISM-SAF eligibility TSS assessment, Radiotherapy or PUVA therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment, Any hematopoietic growth factor < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment, Any major surgical procedure < 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 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 QTcF > 480 msec.
9. Patient has a history of a seizure disorder (eg, epilepsy) or requires antiseizure medication.

The study team makes the final eligibility decision.

Where it's taking place

United States
Canada
United Kingdom
Switzerland

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; Canada; United Kingdom; Switzerland. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.