NCT06548230

A Phase 1B/2A Trial of NADUNOLIMAB in Combination With Azacitidine (With/Without Venetoclax) in Patients With Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To evaluate safety and determine the recommended Phase II dose (RP2D). We hypothesize that targeting leukemia stem/progenitor cells (LSCs) with nadunolimab (IL1RAP antibody) alone or in combination with current therapies of azacitidine (HMA) and venetoclax (Bcl-2 inhibitor), is an effective treatment strategy for high-risk MDS and AML, and with a clinical trial we will establish the safety and the early efficacy of this approach.

Detailed description

Primary Objectives: To determine the safety and recommended phase 2 dose (RP2D) of nadunolimab in combination with azacitidine in intermediate/high/very high risk MDS (International prognostic scoring system revised/IPSS-R) who are untreated or had up to 2 prior treatments (Arm 1) or in combination with azacitidine and venetoclax in patients with relapsed/refractory AML receiving treatment as first or second salvage (Arm 2). Secondary Objectives: To assess the complete remission (CR)+ CR with incomplete count recovery (CRi) + partial remission (PR)+ morphologic leukemia free state (MLFS) rate as per European Leukemia Network 2017 AML response criteria within 6 cycles of treatment initiation in patients with relapsed refractory AML. To assess Overall Response Rate (ORR) defined as \[CR + marrow complete remission (mCR) + partial remission (PR) + CR with partial hematologic recovery (CRh) + hematological improvement (HI)\] as per International Working Group 2023 criteria for MDS in patients with intermediate, high, very high risk MDS (IPSS-R) within 6 cycles of treatment initiation. To determine the duration of response (DOR). Exploratory Objectives: To assess effects on exploratory biomarkers, including serum biomarkers, alterations in hematopoietic subpopulations as measured by multicolor flow cytometry and multimodal single cell analysis, and effects on the leukemic cells as assessed by gene panel analysis and/or single cell DNA-analysis. To evaluate exposure by measuring PK. To evaluate immunogenicity by assessing antidrug antibodies (ADA).

Conditions

• Myelodysplastic Syndrome(MDS)
• Acute Myelogenous Leukemia (AML)

Interventions

Type	Name	Description
DRUG	Nadunolimab	Give by IV
DRUG	Azacitidine	Given by IV
DRUG	Venetoclax	Given by mouth (PO

Timeline

• Start date: 2025-03-05
• Primary completion: 2027-12-01
• Completion: 2029-12-01
• First posted: 2024-08-12
• Last updated: 2026-03-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study