Systemic Mastocytosis With an Associated Hematologic NeoplasmPhase 1NCT06327685
Avapritinib With Decitabine in Patients With SM-AHN
A Phase 1 study testing Avapritinib, Decitabine and Decitabine/Cedazuridine in people with Systemic Mastocytosis With an Associated Hematologic Neoplasm, run by H. Lee Moffitt Cancer Center and Research Institute at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Mastocytosis With an Associated Hematologic Neoplasm
- What is being tested?
- Avapritinib, Decitabine and Decitabine/Cedazuridine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 7 sitesUnited States
- Study dates
- 13 Mar 2024to Mar 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
- Women who are breast feeding.
- Patient is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
- Patient has a primary brain malignancy or metastases to the brain.
- Patient has had a major surgical procedure within 14 days of the first dose of study drug. Surgical procedures such as central venous catheter placement, bone marrow (BM) biopsy, and feeding tube placement are considered minor surgical procedures.
- Patient has eosinophilia and known positivity for the FIP1L1-PGDFRA fusion, unless the patient has demonstrated relapse or progressive disease (PD) on prior imatinib therapy. Patients with eosinophilia (> 1.5 × 109/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
- Patient is participating in another interventional clinical study.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Not yet recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Kristen Pettit, MD
Kristen Pettit, MD
- Not yet recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Daniel DeAngelo, MD, PhD
Daniel DeAngelo, MD, PhD
- Not yet recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Raajit Rampal, MD, PhD
Raajit Rampal, MD, PhD
- Not yet recruiting
Stanford University Medical Center
Palo Alto, California, 94305
Jason Gotlib, MD
Jason Gotlib, MD
- Not yet recruiting
Mayo Clinic - Arizona
Phoenix, Arizona, 85054
Cecilia Arana Yi, MD
Cecilia Arana Yi, MD
- Recruiting
University of Utah Health
Salt Lake City, Utah, 84132
Tsewang Tashi, MD
Tsewang Tashi, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Paul Ciero, 813-745-0774, Paul.Ciero@moffitt.org
Andrew Kuykendall, MD
About this study
Official title: A Phase 1 Study of Avapritinib in Combination With Decitabine in Patients With Systemic Mastocytosis With an Associated Hematologic Neoplasm (SM-AHN)
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.
- Being tested
- Avapritinib, Decitabine, Decitabine/Cedazuridine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvapritinibDrug
Also called Ayvakit
Avapritinib is an oral tyrosine kinase inhibitor.
DecitabineDrug
Also called Dacogen
Decitabine is a nucleoside metabolic inhibitor given intravenously.
Decitabine/CedazuridineCombination product
Also called Inqovi
Decitabine/Cedazuridine is a combination medicine given orally.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Avapritinib; Drug: Decitabine; Combination Product: Decitabine/Cedazuridine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase 2 dose (RP2D)
Recommended phase 2 dose which will be determined by evaluating all safety and efficacy data.
Measured: up to 6 months
Secondary outcomes (3)
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.
Measured: Up to 6 months
Overall Responsive Rate
Overall response rate based on European Competence Network on Mastocytosis-American Initiative in Mast Cell Diseases (ECNM-AIM) criteria.
Measured: Up to 6 months
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.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2024
- Study start13 Mar 2024
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Mastocytosis With an Associated Hematologic NeoplasmStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Blueprint Medicines Corporation
- Responsible party
- Sponsor
- Investigators
- Andrew Kuykendall, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06327685
- Sponsor's protocol ID
- MCC-22318
- Status last verified
- Mar 2026
- First submitted
- 18 Mar 2024
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Avapritinib in Combination With Decitabine in Patients With Systemic Mastocytosis With an Associated Hematologic Neoplasm (SM-AHN)
- ClinicalTrials.gov ID
- NCT06327685
- Acronym / sponsor ID
- MCC-22318
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Blueprint Medicines Corporation
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 25 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: Avapritinib, Drug: Decitabine, Combination Product: Decitabine/CedazuridineParticipants 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 |
| Dose Expansion | Experimental | Drug: Avapritinib, Drug: Decitabine, Combination Product: Decitabine/CedazuridineParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvapritinibAlso: AyvakitAvapritinib is an oral tyrosine kinase inhibitor. | Drug | Dose Escalation, Dose Expansion |
| DecitabineAlso: DacogenDecitabine is a nucleoside metabolic inhibitor given intravenously. | Drug | Dose Escalation, Dose Expansion |
| Decitabine/CedazuridineAlso: InqoviDecitabine/Cedazuridine is a combination medicine given orally. | Combination product | Dose Escalation, Dose Expansion |
Primary outcome
Recommended phase 2 dose (RP2D)
Time frame: up to 6 months
Recommended phase 2 dose which will be determined by evaluating all safety and efficacy data.
3 secondary outcomes
Systemic mastocytosis overall response rate (ORR)
Time frame: Up to 6 months
Overall Responsive Rate
Time frame: Up to 6 months
Incidence and frequency of AEs and changes in vital signs, ECGs, and laboratory tests
Time frame: up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
Related trials for Systemic Mastocytosis With an Associated Hematologic Neoplasm
RecruitingPhase 2
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis
Advanced Systemic Mastocytosis (AdvSM), SM With an Associated Hematologic Neoplasm (SM-AHN)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrew Kuykendall, MD principal investigator
Moffitt Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Avapritinib, Decitabine and Decitabine/Cedazuridine in people with Systemic Mastocytosis With an Associated Hematologic Neoplasm, run by H. Lee Moffitt Cancer Center and Research Institute at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paul Ciero (813-745-0774, Paul.Ciero@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase 2 dose (RP2D) (time frame: up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026.