Avapritinib With Decitabine in Patients With SM-AHN

NCT06327685 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MCC-22318
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Systemic Mastocytosis With an Associated Hematologic Neoplasm

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose (RP2D)

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

  up to 6 months

Secondary Outcomes (3)

• Systemic mastocytosis overall response rate (ORR)

  Up to 6 months

• Overall Responsive Rate

  Up to 6 months

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

  up to 24 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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

Drug: Avapritinib; Drug: Decitabine; Combination Product: Decitabine/Cedazuridine

Dose Expansion

EXPERIMENTAL

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.

Drug: Avapritinib; Drug: Decitabine; Combination Product: Decitabine/Cedazuridine

Interventions

Avapritinib DRUG

Avapritinib is an oral tyrosine kinase inhibitor.

Also known as: Ayvakit

Dose Escalation; Dose Expansion

Decitabine DRUG

Decitabine is a nucleoside metabolic inhibitor given intravenously.

Also known as: Dacogen

Dose Escalation; Dose Expansion

Decitabine/Cedazuridine COMBINATION_PRODUCT

Decitabine/Cedazuridine is a combination medicine given orally.

Also known as: Inqovi

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Willing to receive blood products as deemed clinically necessary.
• Adequate organ and marrow function as defined by the protocol.
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should undergo a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after the last dose of decitabine and 6 weeks after the last dose of avapritinib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study or in the 6 months after last dose of decitabine or 6 weeks after last dose of avapritinib she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study drug administration.

You may not qualify if:

• 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.
• Diagnosis of AML defined as presence of ≥ 20% myeloblasts in the peripheral blood or bone marrow or presence of a myeloid sarcoma.
• Patients who are receiving any other investigational agents or are participating in another interventional study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacytidine, decitabine, cedazuridine, avapritinib, propylene glycol, mannitol (only for patients receiving azacytidine).
• History of intracranial hemorrhage or need for full anticoagulation with warfarin, direct oral anticoagulant, or treatment dose low molecular weight heparin (LMWH), or any condition that, in the investigator's opinion, would put the patient at an increased risk for spontaneous, unprovoked hemorrhage such as: I) Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within one year of the first dose of study drug II) Presence of a vascular aneurysm in the brain III) Known intracranial arteriovenous malformation (AVM).
• Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
• Patient has a QT interval corrected using Fridericia's formula (QTcF) \> 480 msec.
• Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant related immunosuppression.
• Patients receiving any medications or substances that are strong or moderate CYP3A inhibitors or strong or moderate CYP3A inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Participants with uncontrolled intercurrent illness.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because, based on the mechanism of action and data from animal reproduction studies, in utero exposure to avapritinib may cause fetal harm.

Sponsors & Collaborators

• Blueprint Medicines Corporation: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (7)

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

NOT YET RECRUITING

Stanford University Medical Center

Palo Alto, California, 94305, United States

NOT YET RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

University of Utah Health

Salt Lake City, Utah, 84132, United States

RECRUITING

Related Links

• Related Info

MeSH Terms

Interventions

avapritinib; Decitabine; decitabine and cedazuridine drug combination

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Andrew Kuykendall, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Ciero

CONTACT

813-745-0774; Paul.Ciero@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 25, 2024
• Study Start: March 13, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (7)