P2, N=39, Recruiting, University of Maryland, Baltimore | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Jun 2026 --> Jun 2027

We discuss the biological rationale for combination approaches and summarize the key clinical studies that have defined current practice, including trials evaluating FLT3 inhibitors, gemtuzumab ozogamicin, IDH inhibitors, and venetoclax-based strategies. While genotype-directed strategies-such as FLT3 inhibition-have already demonstrated survival benefit, optimal patient selection, treatment sequencing, and duration remain areas of active investigation. Future progress will likely depend on MRD-driven treatment adaptation, improved understanding of clonal evolution, and the development of rational multi-agent combinations capable of achieving deeper and more durable remissions.

P1, N=7, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=36 --> 7 | Trial completion date: Dec 2028 --> Jul 2025 | Active, not recruiting --> Terminated; Upon analysis of the first 7 participants accrued, it was determined that this combination treatment is not efficacious as treatment for patients with relapsed or refractory AML

The risk-based approach and use of targeted therapies in CHIP-AML22 illustrate a shift toward more personalized treatment. Besides improving event-free survival, this study aims to contribute to the international consensus on strategies to reduce toxicity for all patients. The design of this study provides a dynamic framework, allowing for the potential introduction of emerging therapeutic options in the future.

P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=32 --> 0 | Trial completion date: Dec 2034 --> May 2026 | Initiation date: Dec 2027 --> May 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2032 --> May 2026

P2, N=162, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

The anti-CCRL2 ADC demonstrated strong CCRL2-selective cytotoxicity against cell lines derived from MDS/AML patients with TP53 mutations and erythroid features, surpassing the cytotoxic effects observed with gemtuzumab and PBD-conjugated anti-CD33 and anti-CD123 ADCs...This agent also suppressed the leukemic growth of TP53-mutated MDS/AML cell line xenografts, improving mice survival and decreasing the leukemic burden in patient-derived TP53-mutated MDS/AML xenografts. In conclusion, our study introduces CCRL2 as a potential new therapeutic target in high-risk MDS/AML including TP53-mutated subsets.

P1/2, N=92, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

To our knowledge, this is the first study to investigate the prognostic impact of the CD33 rs12459419 SNP per se on outcome and survival in adult AML patients treated with chemotherapy without GO. Validation in larger patient cohorts is required to conclusively rule out a prognostic role of the CD33 rs12459419 SNP in AML.

In summary, trem-cel demonstrated safe, rapid, robust engraftment, and GO maintenance was administered without prolonged hematologic toxicity. ClinicalTrials.gov identifier: NCT04849910 .

P2, N=133, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P3, N=700, Recruiting, University of Birmingham | Active, not recruiting --> Recruiting