Trial Title:
Avapritinib With Decitabine in Patients With SM-AHN
NCT ID:
NCT06327685
Condition:
Systemic Mastocytosis With an Associated Hematologic Neoplasm
Conditions: Official terms:
Neoplasms
Mastocytosis
Mastocytosis, Systemic
Hematologic Neoplasms
Decitabine
Study type:
Interventional
Study phase:
Phase 1
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:
Avapritinib
Description:
Avapritinib is an oral tyrosine kinase inhibitor.
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion
Other name:
Ayvakit
Intervention type:
Drug
Intervention name:
Decitabine
Description:
Decitabine is a nucleoside metabolic inhibitor given intravenously.
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion
Other name:
Dacogen
Intervention type:
Combination Product
Intervention name:
Decitabine/Cedazuridine
Description:
Decitabine/Cedazuridine is a combination medicine given orally.
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion
Other name:
Inqovi
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic - Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Cecilia Arana Yi, MD
Investigator:
Last name:
Cecilia Arana Yi, MD
Email:
Principal Investigator
Facility:
Name:
Stanford University Medical Center
Address:
City:
Palo Alto
Zip:
94305
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jason Gotlib, MD
Investigator:
Last name:
Jason Gotlib, MD
Email:
Principal Investigator
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Caroline Wagstaff
Phone:
813-745-5197
Email:
Caroline.Wagstaff@moffitt.org
Investigator:
Last name:
Andrew Kuykendall, MD
Email:
Principal Investigator
Investigator:
Last name:
Onyee Chan
Email:
Sub-Investigator
Investigator:
Last name:
Rami Komrokji
Email:
Sub-Investigator
Investigator:
Last name:
Timothy Kubal
Email:
Sub-Investigator
Investigator:
Last name:
Jeffrey Lancet
Email:
Sub-Investigator
Investigator:
Last name:
Eric Padron
Email:
Sub-Investigator
Investigator:
Last name:
David Sallman
Email:
Sub-Investigator
Investigator:
Last name:
Alison Walker
Email:
Sub-Investigator
Investigator:
Last name:
Seongseok Yun
Email:
Sub-Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Daniel DeAngelo, MD, PhD
Investigator:
Last name:
Daniel DeAngelo, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Kristen Pettit, MD
Investigator:
Last name:
Kristen Pettit, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Raajit Rampal, MD, PhD
Investigator:
Last name:
Raajit Rampal, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University of Utah Health
Address:
City:
Salt Lake City
Zip:
84132
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Tsewang Tashi, MD
Investigator:
Last name:
Tsewang Tashi, MD
Email:
Principal Investigator
Start date:
March 13, 2024
Completion date:
March 2027
Lead sponsor:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Collaborator:
Agency:
Blueprint Medicines Corporation
Agency class:
Industry
Source:
H. Lee Moffitt Cancer Center and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06327685
https://www.moffitt.org/clinical-trials-research/clinical-trials/
