Avapritinib With Decitabine in Patients With SM-AHN

Conditions

• Systemic Mastocytosis With an Associated Hematologic Neoplasm

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Avapritinib — DRUG
  Avapritinib is an oral tyrosine kinase inhibitor.
• Decitabine — DRUG
  Decitabine is a nucleoside metabolic inhibitor given intravenously.
• Decitabine/Cedazuridine — COMBINATION_PRODUCT
  Decitabine/Cedazuridine is a combination medicine given orally.

Study Details

Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) is a challenging disease to treat. Targeted KIT inhibitors have been approved for this indication based on their ability to control the mastocytosis portion of the disease, but patients frequently experience progression of the concomitant myeloid malignancy (i.e. the AHN). Using a combination approach to treat both aspects of the disease has the potential to provide enhanced disease control; however, overlapping toxicity is a concern. In this study, investigators aim to study the safety and tolerability of combined avapritinib and decitabine for the treatment of SM-AHN.

Key Dates

Start date

Mar 13, 2024

Status verified

Mar 2026

Primary completion

Mar 31, 2027

Completion

Mar 31, 2027

Study Design

Enrollment

34 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Dose Escalation
  Participants will be enrolled in cohorts of size 1-3. Participants will take a combination of Avapritinib and Decitabine. Decitabine will be administered in one of the following forms: I) Decitabine: starting IV dose of 20 mg/m2 on days 1-5 of a 28-day treatment cycle. II) Decitabine/Cedazuridine: starting dose of 35mg/100 mg oral tablet on days 1-5 of a 28-day treatment cycle. The starting dose of Avapritinib for the first cohort of patients will begin at dose level 1 with dose modifications to be made according to a Bayesian design. Avapritnib Dose levels Level -1: 50mg Level 1: 100mg Level 2: 150mg Level 3: 200mg
• Experimental: Dose Expansion
  Participants with baseline platelet count (cycle 1, day 1) ≥ 75 x 10\^9/L will begin the combination of Avapritinib at the dose determined by the dose-finding portion of the study and decitabine or Decitabine/Cedazuridine will be initiated during the first cycle. Participants with a baseline platelet count between 25 x 10\^9/L and 74 x 10\^9/L will receive decitabine or Decitabine/Cedazuridine (choice of investigator) as a single-agent for at least the first two cycles. Starting with cycle 3 and continuing with each subsequent cycle, patients will be eligible to receive Avapritinib in combination with decitabine or Decitabine/Cedazuridine if the platelet count on day 1 of the cycle is ≥ 75 x 10\^9. If the platelet count is \< 75 x 10\^9/L on day 1 of the cycle, patient will receive single-agent Decitabine or Decitabine/Cedazuridine. In the absence of clear disease progression, patients will be treated for at least 6 cycles before being judged to have not responded.

Primary Outcome Measure

Recommended phase 2 dose (RP2D) [ Time Frame: up to 6 months ]

Central Contacts

• Paul Ciero
  813-745-0774
  [email protected]

Locations (7)

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