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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)

Primary Purpose

Myelodysplastic Syndrome, Acute Myeloid Leukemia

Status

Unknown status

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

Panobinostat

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring 60 to 150 Days After Allogeneic Stem Cell Transplantation, High Risk MDS, MDS, AML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

University Hospital Düsseldorf
University Hospital Essen
University Hospital Frankfurt
University Hospital Hamburg-Eppendorf
University Hospital Mainz
University Hospital Marburg

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Panobinostat Arm A

Panobinostat Arm B

Arm Description

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of panobinostat

Dose-limiting toxicity (MTD) of Panobinostat

Secondary Outcome Measures

Cumulative incidence of hematologic relapse and death

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

Time to complete donor chimerism

Cumulative incidence of extensive chronic GvHD

Duration of complete donor chimerism

Cumulative incidence of severe acute GvHD

patient-reported health-related quality of life

Full Information

NCT ID

NCT01451268

First Posted

September 30, 2011

Last Updated

March 19, 2018

Sponsor

Johann Wolfgang Goethe University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01451268

Brief Title

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)

Acronym

PANOBEST

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Unknown status

Study Start Date

January 2011 (Actual)

Primary Completion Date

April 2018 (Anticipated)

Study Completion Date

April 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Johann Wolfgang Goethe University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome, Acute Myeloid Leukemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Panobinostat Arm A

Arm Type

Experimental

Arm Title

Panobinostat Arm B

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Panobinostat

Other Intervention Name(s)

LBH589

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Panobinostat

Other Intervention Name(s)

LBH589

Intervention Description

Start of Arm B after completion of Arm A; initial dose-level: one level below MTD of Arm A; 10mg upto 60mg Panobinostat dose escalation in consequent cohorts; frequency: three times a week, every other week; duration: one year

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD) of panobinostat

Time Frame

after 28 days of administration

Title

Dose-limiting toxicity (MTD) of Panobinostat

Time Frame

after 28 days of administration

Secondary Outcome Measure Information:

Title

Cumulative incidence of hematologic relapse and death

Time Frame

one year after HSCT

Title

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

Time Frame

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

Title

Time to complete donor chimerism

Time Frame

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

Title

Cumulative incidence of extensive chronic GvHD

Time Frame

one year after HSCT

Title

Duration of complete donor chimerism

Time Frame

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

Title

Cumulative incidence of severe acute GvHD

Time Frame

one year after HSCT

Title

patient-reported health-related quality of life

Time Frame

after 3 months of administration and one month after last intake of study drug

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gesine Bug, MD

Organizational Affiliation

Johann Wolfgang Goethe University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Düsseldorf

City

Düsseldorf

ZIP/Postal Code

40225

Country

Germany

Facility Name

University Hospital Essen

City

Essen

ZIP/Postal Code

45147

Country

Germany

Facility Name

University Hospital Frankfurt

City

Frankfurt am Main

ZIP/Postal Code

60590

Country

Germany

Facility Name

University Hospital Hamburg-Eppendorf

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

University Hospital Mainz

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

University Hospital Marburg

City

Marburg

ZIP/Postal Code

35043

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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)

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