Ignite Creation Date:
2025-12-24 @ 11:17 PM
Ignite Modification Date:
2026-01-06 @ 12:52 PM
Study NCT ID:
NCT06523556
Status:
RECRUITING
Last Update Posted:
2025-06-26
First Post:
2024-07-09
Is Gene Therapy:
True
Has Adverse Events:
False
Brief 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
Sponsor:
Uma Borate
Organization:
Study Overview
Official Title:
Phase 1b/2 Study of Axatilimab (SNDX-6352) + Azacitidine (AZA) in Advanced Phase MPN, MPN/MDS Overlap or High-Risk CMML
Status:
RECRUITING
Status Verified Date:
2025-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2024-05515 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View |