Trial Title:
Study of Elenestinib (BLU-263) in Advanced Systemic Mastocytosis (AdvSM) and and Other KIT Altered Hematologic Malignancies
NCT ID:
NCT05609942
Condition:
Advanced Systemic Mastocytosis
Conditions: Official terms:
Hematologic Neoplasms
Mastocytosis
Mastocytosis, Systemic
Azacitidine
Conditions: 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
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BLU-263
Description:
BLU-263 Oral Tablets
Arm group label:
Combination therapy
Arm group label:
Monotherapy
Other name:
elenestinib
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Azacitidine powder for suspension for intravenous infusion / subcutaneous injection
Arm group label:
Combination therapy
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. 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.
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).
Criteria for eligibility:
Criteria:
Key Inclusion Criteria :
- 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:
1. Aggressive SM (ASM).
2. 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.
3. Mast cell leukemia (MCL), including diagnoses with an AHN component, that does not
require a C-finding.
4. 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).
Key Exclusion Criteria:
- 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.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Stanford Cancer Institute
Address:
City:
Palo Alto
Zip:
94305
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Facility:
Name:
Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Facility:
Name:
Antwerp University Hospital
Address:
City:
Edegem
Zip:
2650
Country:
Belgium
Status:
Recruiting
Facility:
Name:
University Hospital Ghent
Address:
City:
Ghent
Zip:
9000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
CHU Caen - Institut d'Hematologie de Basse Normandie
Address:
City:
Caen
Zip:
14033
Country:
France
Status:
Recruiting
Facility:
Name:
University Medical Centre Mannheim
Address:
City:
Mannheim
Zip:
68167
Country:
Germany
Status:
Recruiting
Facility:
Name:
Maastricht University Medical Center
Address:
City:
Maastricht
Zip:
6229 HX
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
Oslo University Hospital
Address:
City:
Oslo
Zip:
0450
Country:
Norway
Status:
Recruiting
Facility:
Name:
Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast)
Address:
City:
Toledo
Zip:
45071
Country:
Spain
Status:
Recruiting
Start date:
September 25, 2023
Completion date:
November 30, 2029
Lead sponsor:
Agency:
Blueprint Medicines Corporation
Agency class:
Industry
Source:
Blueprint Medicines Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05609942
