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.
Diagnosis
Arm 1: Diagnosis of MDS intermediate/high/very high risk by Revised International Prognostic Scoring System (IPSS-R), Untreated or up to 2 prior treatments.
Arm 2: Diagnosis of relapsed/refractory AML (per European Leukemia Network 2022) [26] receiving treatment as salvage 1-2. MDS or CMML treated with hypomethylating agent (HMA) therapies who progress to AML and have no available better therapies or are not candidates for available therapies, will be eligible at the time of progression to AML.
Patients aged ≥18 years
Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study.
Patients on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.
Prior organ transplantation including allogenic stem-cell transplantation within 3 months prior to planned enrollment, active graft versus host disease (GVHD) >Grade 1 or requiring transplant-related immunosuppression with the exception of low dose cyclosporine and tacrolimus.
Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.