Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)

Phase I/II Study With Oral Panobinostat Maintenance Therapy Following Allogeneic Stem Cell Transplantation in Patients With High Risk MDS or AML (PANOBEST)

The study's primary objective is to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Panobinostat when administered within 150 days after hematopoietic stem cell transplantation (HSCT) and given in conjunction with standard immunosuppressive therapy after HSCT for patients with high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML).

Secondary objectives are

• To determine safety and tolerability of panobinostat
• To determine overall and disease-free survival at 12 months after HSCT
• To evaluate immunoregulatory properties of panobinostat
• To evaluate patient-reported health-related quality of life (HRQL)

The hypothesis of this study is that panobinostat can be an effective drug in preventing relapse of MDS and AML patients with high-risk features after hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC-HSCT) while at the same time reducing graft-versus-host disease (GvHD) with preservation of graft-versus-leukemia (GvL) effect.

Inclusion Criteria:

• AML (except acute promyelocytic leukemia, AML M3) with high-risk features defined as one or more of the following criteria:

  • refractory to or relapsed after at least one cycle of standard chemotherapy
  • > 10% bone marrow blasts at day 15 of the first induction cycle
  • adverse risk cytogenetics including complex karyotype (≥ 3 abnormalities or abnormalities of chromosomes 3, 5 or 7) regardless of stage
  • secondary to MDS or radio-/chemotherapy or

• MDS RAEB according to the WHO classification or intermediate-2 or high-risk according to IPSS or

• Chronic myelomonocytic leukemia (CMML) with ≥ 5% bone marrow blasts and

  • Allogeneic HSCT with reduced intensity conditioning (see Section 15.1 for definition) performed within 60 - 150 days prior to study entry
  • Complete hematologic remission documented by bone marrow aspiration within 28 days prior to study entry

Exclusion Criteria:

• Active acute GvHD overall grade 2 - 4
• Prior treatment with a deacetylase (DAC) inhibitor
• Patients with impaired cardiac function or other concurrent severe and/or uncontrolled medical conditions
• Clinical symptoms suggesting central nervous system (CNS) leukemia
• Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat