Trial Title:
Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia
NCT ID:
NCT06523556
Condition:
Atypical Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm
Recurrent Myelodysplastic/Myeloproliferative Neoplasm
Recurrent Myeloproliferative Neoplasm
Refractory Chronic Myelomonocytic Leukemia
Refractory Myelodysplastic/Myeloproliferative Neoplasm
Refractory Myeloproliferative Neoplasm
Conditions: Official terms:
Leukemia
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Recurrence
Azacitidine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Axatilimab
Description:
Given IV
Arm group label:
Phase I (Axatilimab)
Arm group label:
Phase II (Axatilimab and azacitidine)
Other name:
Anti-M-CSFR Monoclonal Antibody SNDX-6352
Other name:
SNDX 6352
Other name:
SNDX-6352
Other name:
SNDX6352
Other name:
UCB6352
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Given IV or SC
Arm group label:
Phase II (Axatilimab and azacitidine)
Other name:
5 AZC
Other name:
5-AC
Other name:
5-Azacitidine
Other name:
5-Azacytidine
Other name:
5-AZC
Other name:
Azacytidine
Other name:
Azacytidine, 5-
Other name:
Ladakamycin
Other name:
Mylosar
Other name:
U-18496
Other name:
Vidaza
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Phase I (Axatilimab)
Arm group label:
Phase II (Axatilimab and azacitidine)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration and Biopsy
Description:
Undergo bone marrow biopsy and aspiration
Arm group label:
Phase I (Axatilimab)
Arm group label:
Phase II (Axatilimab and azacitidine)
Intervention type:
Other
Intervention name:
Survey Administration
Description:
Ancillary study
Arm group label:
Phase II (Axatilimab and azacitidine)
Summary:
This phase Ib/II trial tests the best dose of axatilimab and effectiveness of axatilimab
with or without azacitidine for the treatment of patients with advanced phase
myeloproliferative neoplasms (MPN), myeloproliferative neoplasm/myelodysplastic syndrome
(MPN/MDS) overlap or high risk chronic myelomonocytic leukemia (CMML). Axatilimab is an
antibody that is cloned from a single white blood cell that is known to be able to
recognize cancer cells and block a protein on the surface of the white blood cells that
may be involved in cancer cell growth. By blocking the proteins, this may slow or halt
the growth of the cancer. Azacitidine is in a class of medications called
antimetabolites. It works by stopping or slowing the growth of cancer cells. Giving
axatilimab with or without azacitidine may be safe and effective in treating patients
with advanced phase MPN, MPN/MDS overlap or high risk CMML.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) of axatilimab in relapsed or
refractory patients with advanced phase MPN, MPN/MDS overlap or high-risk CMML.
II. To evaluate the overall response rate of axatilimab + azacitidine (AZA) in newly
diagnosed patients with advanced phase MPN, MPN/MDS overlap or high-risk CMML using
Savona response criteria.
SECONDARY OBJECTIVES:
I. Determine the safety and tolerability of axatilimab + azacitidine combination therapy
in those with newly diagnosed advanced phase MPN, MPN/MDS overlap or high-risk CMML.
II. Determine the quality of life in patients receiving axatilimab + AZA using a Modified
Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).
III. Determine the effect of axatilimab + azacitidine on symptom relief which will be
measured by transfusion burden (platelet and/or packed red blood cell), time in hospital,
and immune related side effects specifically reactivation of tuberculosis (TB),
infusion-related reactions, hepatotoxicity, pneumonia, pyrexia, sepsis, shortness of
breath (SBO), hemoptysis, periorbital edema, fatigue, and pancreatitis.
EXPLORATORY OBJECTIVES:
I. To assess the pharmacokinetics of axatilimab in combination with AZA. II. To describe
the prevalence and trajectories of patients' physical activity during treatment.
III. To perform detailed correlative studies related to genetic, biochemical, and
immunologic changes that occur with axatilimab in combination with AZA.
OUTLINE: This is a phase I, dose-escalation study of axatilimab followed by a phase II
study.
PHASE I: Patients receive axatilimab intravenously (IV) over 30 minutes on days 1 and 15
of each cycle. Cycles repeat every 28 days in the absence of disease progression or
unacceptable toxicity. At time of phase Ib completion, patients with clinical improvement
may transition to phase II. Patients undergo bone marrow biopsy and aspiration and blood
sample collection throughout the study.
PHASE II: Patients receive axatilimab IV over 30 minutes on days 1 and 15 and azacitidine
IV over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle. Cycles repeat
every 28 days for up to 4 cycles in the absence of disease progression or unacceptable
toxicity. Patients who achieve partial response (PR) or better may continue for up to 24
total cycles. Patients who achieve less than PR receive 2 additional cycles and, if PR or
better is achieved, may complete up to 24 total cycles. Patients undergo bone marrow
biopsy and aspiration and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days and then every 6
months for up to 24 months after last dose of study medication.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study
- Age ≥ 18 years at the date of signing the informed consent form (ICF)
- Morphologically confirmed diagnosis of the following based on 2016 World Health
Organization (WHO) classification (Arber et al 2016): Phase 1b, patients with
relapsed or refractory of any of the following; phase 2, patients with newly
diagnosed of any of the following:
- Chronic myelomonocytic leukemia (CMML), classified as intermediate-2, OR
high-risk per the CMML Specific Prognostic Scoring System (CPSS) Molecular
Model
- Atypical chronic myelocytic leukemia (aCML)
- MDS/MPN unclassified (MDS/MPN-U)
- Myeloproliferative neoplasm accelerated phase (MPN-AP)
- MPN-AP requires a previous diagnosis of polycythemia vera (PV), essential
thrombocythemia (ET), or primary myelofibrosis (PMF) with intermediate-2 or
high risk disease according to International Prostate Symptom Score (IPSS) as
well as progression on or failure to respond to at least one line of therapy.
- Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and
thrombocytosis (MDS/MPN-RS-T) or MDS/MPN with SF3B1 mutation and thrombocytosis
(MDS/MPN-SF3B1-T).
- Not suitable for immediate myeloablative/intensive chemotherapy based on
investigator assessment of age, comorbidities, local guidelines, institutional
practice (any or all of these)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper
limit of normal (ULN)
- Total bilirubin ≤ 1.5 × ULN (except in the setting of isolated Gilbert syndrome)
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m^2 (estimation based on
Modification of Diet in Renal Disease [MDRD] formula, by local laboratory)
- Patient is able to communicate with the investigator and has the ability to comply
with the requirements of the study procedures
- Women of childbearing potential and men, if not surgically sterilized, should use
adequate contraception from 14 days prior to study entry and until 90 days after the
last follow-up visit. Adequate contraception is defined as using hormonal
contraceptives or an intrauterine device combined with at least 1 of the following
forms of contraception: a diaphragm or cervical cap, or a condom
Exclusion Criteria:
- Previous treatment for MPN or MDS/MPN overlap with chemotherapy or other
antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such
as decitabine or azacitidine or INQOVI (oral decitabine) (patients who had up to 2
cycles of hypomethylating agents [HMAs] can be included). However, previous
treatment with hydroxyurea and/or ruxolitinib is permitted
- Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and
extra-medullary AML based on WHO 2016 classification (Arber et al 2016)
- Patients who are candidates for myeloablative or intensive chemotherapy treatment or
who do not provide consent for this treatment
- History of organ transplant or allogenic hematopoietic stem cell transplant
- Participants with prior malignancy, except:
- Participants with history of adequately treated malignancy for which no
anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is
ongoing or required during the course of the study.
- Participants who are receiving adjuvant therapy such as hormone therapy are
eligible. However, participants who developed therapy related neoplasms are not
eligible
- Previous known allergy/sensitivity to components of axatilimab
- History of acute or chronic pancreatitis
- History of myositis
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Uma M. Borate
Phone:
614-293-3316
Email:
Uma.Borate@osumc.edu
Investigator:
Last name:
Uma M. Borate
Email:
Principal Investigator
Start date:
August 2, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Uma Borate
Agency class:
Other
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06523556
http://cancer.osu.edu
