Avapritinib With Decitabine in Patients With SM-AHN

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorH. Lee Moffitt Cancer Center and Research Institute

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis of SM-AHN defined by World Health Organization 2022 criteria.

ECOG 0-3

Ability to understand and the willingness to sign a written informed consent.

Ability to adhere to study visit schedule and other protocol requirements.

Disqualifiers

History of decitabine use with documented disease progression of AHN by 2006 IWG MDS response criteria while on decitabine.

History of avapritinib use with documented progression of mastocytosis while on avapritinib per m-IWG-MRT-ECNM criteria.

History of treatment with decitabine in combination with avapritinib.

Use of azacitidine within 4 weeks of first dose of study drug.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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.

Treatment groups

34 Participants
are divided into 2 treatment groups
Group A: Dose EscalationExperimental treatment 3 interventions
Group B: Dose ExpansionExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Recommended phase 2 dose (RP2D)

Recommended phase 2 dose which will be determined by evaluating all safety and efficacy data.

Time frame
up to 6 months

Secondary outcomes

1

Systemic mastocytosis overall response rate (ORR)

Overall response rate by modified International Working Group-Myeloproliferative Neoplasms Research and treatment and European Competence Network on Mastocytosis (m-IWG-MRT-ECNM) consensus criteria.

Time frame
Up to 6 months
2

Overall Responsive Rate

Overall response rate based on European Competence Network on Mastocytosis-American Initiative in Mast Cell Diseases (ECNM-AIM) criteria.

Time frame
Up to 6 months
3

Incidence and frequency of AEs and changes in vital signs, ECGs, and laboratory tests

Incidence and frequency of AEs and changes in vital signs, ECGs, and laboratory tests according to CTCAE v5.0.

Time frame
up to 24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

H. Lee Moffitt Cancer Center and Research Institute

Lead sponsor

Blueprint Medicines Corporation

Collaborator