Clinical trials specifically targeting the patient population with CMML are the gold standard.

Increased commitment to preclinical research investigating CMML is required to identify biologically rationale therapies for clinical investigation in this unique disease.

All patients with CMML should be treated in clinical trials, when possible.

Careful consideration should be taken regarding study design and selection of the target population. Studies should be simple and enroll as broad of a population as is appropriate (unique for each investigational agent) to promote successful accrual.

Early phase studies should use adaptive study designs.

Early phase studies should identify the optimal biologic dose.

MDS/MPN-specific response criteria should be used to assess efficacy.

PRO measures should be incorporated into all studies.

The use of HMAs in the clinical trial setting is complex given the lack of data supporting a disease-modifying effect in CMML. Thoughtful consideration is required regarding the role of HMA in requirements for prior therapy, backbones for combination therapy, and selection of comparator arms, and should not be considered paradigmatic.

Close collaboration is necessary among the CMML community in executing clinical trials and collecting real-world data.

Investigators should consult with the FDA early in study development.