European Intergroup Trial on panobinostat maintenance after HSCT for high-risk AML and MDS - A randomized, multicenter phase III study to assess the efficacy of panobinostat maintenance therapy vs. standard of care following allogeneic stem cell transplantation in patients with high-risk AML or MDS (ETAL-4 / HOVON-145)

Collectively, the PANOBEST and HOVON-116 studies provide the rationale for a
European prospective randomized trial of panobinostat as post-transplant
intervention with the aim to determine the definite role of DACi maintenance
for high-risk myeloid malignancies (Table 7). Together with available data from
clinical trials of post-transplant HMA, they support a prophylactic versus a
pre-emptive strategy, particularly given the limited availability of highly
sensitive and clinically validated MRD markers and the lower clinical burden in
the MRD negative setting. Following HSCT, a timely initiation of panobinostat
treatment is needed to make the potentially beneficial therapy accessible to
patients with aggressive diseases, but the panobinostat dose must be chosen
carefully, taking into account the vulnerability of the hematopoietic and
immune reconstitution in the early post-transplant period.

Primary objective
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To determine the efficacy of panobinostat maintenance therapy versus standard
of care administered to patients with high-risk MDS or AML in complete
hematologic remission after an allogeneic hematologic stem cell transplantation
(HSCT)

Secondary objectives

- To assess the safety and tolerability of panobinostat maintenance therapy
after HSCT compared with standard of care
- To evaluate HRQoL of patients under panobinostat maintenance therapy after
HSCT
- To study the treatment effect in subgroups of patients defined by treatment
approach (i.e. HOVON-approach vs. RIC vs MAC conditioning), donor type
(HLA-compatible versus haploidentical) and molecular distinct subgroups of
AML/MDS

Multicenter, randomized phase III trial

Patients will receive panobinostat at a starting dose of 20 mg, once a day,
three days per week, every other week. Study treatment will be started within 7
days after randomization and continued for a maximum of one year after HSCT in
the absence of relapse or unacceptable toxicity.

Although alloHSCT is standard care in high risk AML or MDS, the incidence of
relapse after alloHSCT is high. We recently showed that treatment with
panobinostat post transplant may prevent relapse. The risk associated with
panobinostat treatment are opportunistic infections, associated with
neutropenia and lymphopenia.