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)

NCT01451268 | Unknown Phase 1

• 1 other identifier: CLBH589 BDE05T
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Keywords

60 to 150 Days After Allogeneic Stem Cell Transplantation; High Risk MDS; MDS; AML

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of panobinostat

  after 28 days of administration

• Dose-limiting toxicity (MTD) of Panobinostat

  after 28 days of administration

Secondary Outcomes (7)

• Cumulative incidence of hematologic relapse and death

  one year after HSCT

• Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy

  patients will be followed for up to 2 years depending on the duration of study participation

• Time to complete donor chimerism

  patients will be followed for up to 2 years depending on the duration of study participation

• Cumulative incidence of extensive chronic GvHD

  one year after HSCT

• Duration of complete donor chimerism

  patients will be followed for up to 2 years depending on the duration of study participation

Study Arms (2)

Panobinostat Arm A

EXPERIMENTAL

Drug: Panobinostat

Panobinostat Arm B

EXPERIMENTAL

Drug: Panobinostat

Interventions

Panobinostat DRUG

10mg upto 40mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every week; duration: one year

Also known as: LBH589

Panobinostat Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johann Wolfgang Goethe University Hospital: lead

Study Sites (6)

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

Location

University Hospital Essen

Essen, 45147, Germany

Location

University Hospital Frankfurt

Frankfurt am Main, 60590, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

University Hospital Mainz

Mainz, 55131, Germany

Location

University Hospital Marburg

Marburg, 35043, Germany

Location

Related Links

• Trial register of the Kompetenznetz Leukämien, additional trial information

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gesine Bug, MD

  Johann Wolfgang Goethe University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior physician hematology

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 13, 2011
• Study Start: January 1, 2011
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: March 20, 2018

Record last verified: 2018-03

Locations

DE (6)