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) (PANOBEST)

Johann Wolfgang Goethe University Hospital

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Myelodysplastic Syndrome

Acute Myeloid Leukemia

Treatments

Drug: Panobinostat

Study type

Interventional

Funder types

Other

Identifiers

NCT01451268

CLBH589 BDE05T

Details and patient eligibility

About

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.

Enrollment

62 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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