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)

• Status: Unknown status
• Trial end date: 2018-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johann Wolfgang Goethe University Hospital
• Treatments: Panobinostat

Criteria

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