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Advanced Systemic MastocytosisPhase 1AZURENCT05609942

Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies

A Phase 1 study testing BLU-263 and Azacitidine in people with Advanced Systemic Mastocytosis, run by Blueprint Medicines Corporation at 11 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The goal of this clinical trial is to evaluate elenestinib (BLU-263) in participants with Advanced Systemic Mastocytosis (AdvSM), SM with an associated hematologic neoplasm (SM-AHN), and other hematologic malignancies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Systemic Mastocytosis
What is being tested?
BLU-263 and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
11 sitesin 7 countries
Study dates
25 Sep 2023to 10 Mar 2025
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
  • Participant must have a new Bone Marrow (BM) biopsy or may use archival tissue if taken within 56 days prior to C1D1 and participant must be willing to have follow-up BM Biopsies.
  • Participants receiving antineoplastic therapy within the preceding 12 weeks must have discontinued therapy due to disease progression, refractory disease, lack of efficacy, or intolerance.
  • Participants treated with 1 prior selective KIT inhibitor (such as avapritinib or CGT9486) will be permitted on study after confirmation of KIT D816V mutation and with written approval of the study Sponsor. Participants who discontinued treatment with a prior selective KIT inhibitor due to a severe AE that was thought to be related to prior treatment will not be eligible to participate in the study.
  • Arm 1 (Monotherapy): Participants must have one of the following AdvSM diagnoses, based on World Health Organization (WHO) diagnostic criteria.
  • Before enrollment, diagnosis of AdvSM must be confirmed based on Central Pathology Laboratory assessment of BM:
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  • Aggressive SM (ASM).
  • SM-AHN that in the opinion of the Investigator is not considered to be a candidate for Hypomethylating agent (HMA) monotherapy. Incidental indolent, low-grade lymphoid AHNs (eg, chronic lymphocytic leukemia) not requiring treatment are eligible.
  • Mast cell leukemia (MCL), including diagnoses with an AHN component, that does not require a C-finding.
  • Upon discussion with the Sponsor, other relapsed or refractory hematologic neoplasms with evidence of aberrant KIT or PDGFR may be considered for enrollment. (eg, participants with chronic myeloid neoplasms, such as subvariants of MDS/MPN that harbor activating KIT exon 17 mutations but do not fulfill the diagnostic criteria of SM-AHN, and participants with myeloid/lymphoid neoplasms with PDGFRa/b fusion genes and mutations conferring resistance to imatinib, such as T674I or D842V).

Who cannot join

  • Diagnosis of a Philadelphia chromosome positive malignancy
  • Acute myeloid leukemia.
  • If the participant is receiving corticosteroids, and the dose has not been stable for ≥7 days.
  • Within the 14 days prior to enrollment, participant has received any antineoplastic therapy (including midostaurin, avapritinib and other tyrosine kinase inhibitors [TKIs]) or an investigational agent.
  • Participant has received hydroxyurea within 7 days prior to the first dose of elenestinib (BLU-263).
  • Participant received prior HMA therapy (e.g., azacitidine, decitabine) for the current diagnosis.
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  • Participant must not be eligible for allogenic hematopoietic stem cell transplantation.
  • Participant received prior radiotherapy within 14 days of screening BM biopsy.
  • Participant received any hematopoietic growth factor (except erythropoietin) within 14 days of screening BM biopsy, or requiring growth factors to maintain adequate neutrophil or platelet levels.
  • Those participants maintained on a chronic dose of erythropoietin, whose hemoglobin is stable, and dose of erythropoietin has not been changed in the prior 28 days are allowed on study.
  • Participant received >1 prior selective KIT inhibitor (eg: avapritinib or bezuclastinib).
  • Participant have any of the following laboratory abnormalities on last laboratory assessment within 14 days prior to the first dose of initiation of study drug: a. Alanine aminotransferase and aspartate aminotransferase > 3 × ULN; > 5 × ULN if associated with clinically suspected liver infiltration by mastocytosis or another disease for which the patient enrolled into the study b. Total bilirubin > 1.5 × ULN; > 3 × ULN if associated with liver infiltration by the disease being treated or in the presence of Gilbert's Disease. (In the case of Gilbert's disease, a direct bilirubin > 2.0 ULN would be an exclusion) c. Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 40 mL/min d. Absolute neutrophil count < 0.5 × 10^9/L
  • Participant has had a major surgical procedure within 14 days of the first dose of study drug.
  • History of another primary malignancy that has been diagnosed or required therapy within 1 year prior to the first dose of study drug. The following are exempt from the 1-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, GI stromal tumor, and completely resected carcinoma in situ of any site.
  • Mean resting QTcF > 480 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
  • Clinically significant, uncontrolled, cardiovascular disease.
  • Arm 1 (Monotherapy):
  • Myelodysplastic Syndrome (MDS) that is very high- or high-risk as defined by the International Prognostic Scoring System for Myelodysplastic Syndromes-Revised (IPSS-R).
  • A myeloid AHN with ≥10% BM or peripheral blood blasts.
  • Platelet count <50 x 10^9/L (within 4 weeks prior to the first dose of study drug) or receiving platelet transfusions or thrombopoietin receptor agonists (TPO-RA) within the prior 14 days.

Trial locations and contacts

11 sites in 7 countries.

11 sites in 7 countries

United States4 sites
  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Stanford Cancer Institute

    Palo Alto, California, 94305

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

Other trials in United States

Belgium2 sites
  • Antwerp University Hospital

    Edegem, 2650

  • University Hospital Ghent

    Ghent, 9000

Other trials in Belgium

France1 site
  • CHU Caen - Institut d'Hematologie de Basse Normandie

    Caen, 14033

Other trials in France

Germany1 site
  • University Medical Centre Mannheim

    Mannheim, 68167

Other trials in Germany

Netherlands1 site
  • Maastricht University Medical Center

    Maastricht, 6229 HX

Other trials in Netherlands

Norway1 site
  • Oslo University Hospital

    Oslo, 0450

Other trials in Norway

Spain1 site
  • Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast)

    Toledo, 45071

Other trials in Spain

About this study

Official title: A Phase 1/2, Open-label, 2-arm Study Evaluating BLU-263 as Monotherapy and in Combination With Azacitidine, in Patients With KIT Altered Hematologic Malignancies

The goal of this clinical trial is to evaluate elenestinib (BLU-263) in participants with Advanced Systemic Mastocytosis (AdvSM), SM with an associated hematologic neoplasm (SM-AHN), and other hematologic malignancies. The main questions it aims to answer are:

  • Determine Recommended Dose of elenestinib (BLU-263) monotherapy for participants with AdvSM
  • Safety and tolerability of elenestinib (BLU-263) monotherapy
  • Efficacy of elenestinib (BLU-263) monotherapy in participants with AdvSM
  • Determine Recommended Dose of elenestinib (BLU-263) in combination with azacitidine in participants with AdvSM
  • Safety and tolerability of elenestinib (BLU-263) in combination with azacitidine
  • Efficacy of elenestinib (BLU-263) in combination with azacitidine in participants with AdvSM

The estimated study duration for each participant will be approximately 4 years: 2 years of treatment followed by 2 years of follow-up. Participants may be required to attend monthly visits for the first six months, followed by quarterly visits for the remainder of the study.

Read the detailed description

Systemic mastocytosis includes five major subtypes: Indolent SM (ISM), SM with an associated hematologic neoplasm (SM-AHN), aggressive SM (ASM), and MC leukemia (MCL). In 2016, the smoldering subtype of SM, a former provisional ISM subvariant, was designated as a distinct variant of SM by the World Health Organization (WHO). Aggressive SM, SM-AHN, and MCL together are referred to as Advanced SM (AdvSM).

Being tested
BLU-263, Azacitidine
Keywords
BLU-263, elenestinib, azacitidine, AdvSM, KIT D816V, Advanced systemic mastocytosis, Mast cell leukemia, MCL, Systemic mastocytosis, SM, SM-AHN, CMML-2, Myelodysplastic/myeloproliferative neoplasms, MDS/MPN, Myeloid neoplasms, ASM
Medical subject headings
Mastocytosis, Systemic, Leukemia, Mast-Cell, Myelodysplastic-Myeloproliferative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BLU-263Drug

    Also called elenestinib

    BLU-263 Oral Tablets

  • AzacitidineDrug

    Azacitidine powder for suspension for intravenous infusion / subcutaneous injection

Study groups in NCT05609942
Study groupRoleWhat they receive
MonotherapyExperimentalParticipants with AdvSM (ASM, SM-AHN, or MCL) will receive BLU-263 monotherapy.
Receives: Drug: BLU-263
Combination therapyExperimentalParticipants with high risk and very high risk systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) of non-MC lineage will receive BLU-263 in combination with azacitidine.
Receives: Drug: BLU-263; Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation: Number of Dose-limiting Toxicities (DLTs) (monotherapy only)

    Monotherapy: The Recommended Dose (RD) will be primarily determined by the number of DLTs in the first 28 days of treatment with elenestinib (BLU-263) monotherapy.

    Measured: 28 Days

  2. Dose Escalation: Number of DLTs (combination therapy only)

    Combination therapy: The RD will be primarily determined by the number of DLTs (during 28 days starting from Day 15 of C1 or Day 15 of C2) with elenestinib (BLU-263) in combination with azacitidine.

    Measured: 28 Days

  3. Dose Escalation and Expansion: Pure Pathological Response (PPR) Rate for SM in Selective KIT Inhibitor-naïve Participants (monotherapy only)

    PPR Rate is defined as complete remission (resolution of palpable splenomegaly/hepatomegaly) (CR) + complete remission with partial recovery of peripheral blood counts (CRh) + partial remission (≥35% reduction in spleen volume) (PR)

    Measured: Up to approximately 4 years

  4. Dose Escalation and Expansion: Number of Participants with Adverse Events (AEs)

    Measured: Up to approximately 4 years

  5. Dose Escalation and Expansion: Number of Participants with Serious Adverse Events (SAEs)

    Measured: Up to approximately 4 years

Secondary outcomes (22)
  1. Dose Escalation and Expansion: Overall Response Rate (ORR) for AdvSM using modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) (monotherapy only)

    ORR is defined as CR + CRh + PR + Clinical Improvement (CI)

    Measured: Up to approximately 4 years

  2. Dose Escalation and Expansion: ORR for SM Using Modified IWG-MRT-ECNM (combination therapy only)

    Measured: Up to approximately 4 years

  3. Dose Escalation and Dose Expansion: Maximum Plasma Concentration (Cmax) of BLU-263

    Measured: Up to approximately 4 years

  4. Dose Escalation and Dose Expansion: Cmax of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  5. Dose Escalation and Dose Expansion: Time to Maximum Concentration (Tmax) of BLU-263

    Measured: Up to approximately 4 years

  6. Dose Escalation and Dose Expansion: Tmax of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  7. Dose Escalation and Dose Expansion: Area Under the Curve From Time Zero to 24 Hours (AUC(0-24)) of BLU-263

    Measured: Up to approximately 4 years

  8. Dose Escalation and Dose Expansion: AUC(0-24) of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  9. Dose Escalation and Dose Expansion: Apparent Volume of Distribution (Vz/F) of BLU-263

    Measured: Up to approximately 4 years

  10. Dose Escalation and Dose Expansion: Vz/F of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  11. Dose Escalation and Dose Expansion: Terminal Elimination Half-life (t1/2) of BLU-263

    Measured: Up to approximately 4 years

  12. Dose Escalation and Dose Expansion: t1/2 of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  13. Dose Escalation and Dose Expansion: Apparent Oral Clearance (CL/F) of BLU-263

    Measured: Up to approximately 4 years

  14. Dose Escalation and Dose Expansion: CL/F of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  15. Dose Escalation and Dose Expansion: Accumulation Ratio of BLU-263

    Measured: Up to approximately 4 years

  16. Dose Escalation and Dose Expansion: Accumulation Ratio of Azacitidine (combination therapy only)

    Measured: Up to approximately 4 years

  17. Dose Escalation and Expansion: Overall Survival (OS) (monotherapy only)

    Measured: Up to approximately 4 years

  18. Dose Escalation and Expansion: Time to Response (TtR) (monotherapy only)

    Measured: Up to approximately 4 years

  19. Dose Escalation and Expansion: Duration of Response (DOR) (monotherapy only)

    Measured: Up to approximately 4 years

  20. Dose Escalation and Expansion: Progression-Free Survival (PFS) (monotherapy only)

    Measured: Up to approximately 4 years

  21. Dose Escalation and Expansion: Proportion of Participants Pursuing Stem Cell Transplant (monotherapy only)

    Measured: Up to approximately 4 years

  22. Dose Escalation and Expansion: PPR Rate for SM (combination therapy only)

    Measured: Up to approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2022
  2. Study start25 Sep 2023
  3. Primary completion14 Jan 2025
  4. Study completion10 Mar 2025

Why it stopped: Terminated - alignment of strategic priorities

Resources

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05609942
Sponsor's protocol ID
BLU-263-2101
Other IDs
2022-001535-87
Acronym
AZURE
Status last verified
Mar 2025
First submitted
2 Nov 2022
Last updated
10 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BLU-263 and Azacitidine in people with Advanced Systemic Mastocytosis, run by Blueprint Medicines Corporation at 11 sites in 7 countries.

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 10 inclusion and 20 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: stopped early, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Belgium, France, Germany, Netherlands and 2 more countries. 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?

The study was stopped early (reason given: Terminated - alignment of strategic priorities). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: Number of Dose-limiting Toxicities (DLTs) (monotherapy only) (time frame: 28 Days). The study lists 5 primary outcomes in all. 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 10 Apr 2025.

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