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)

Acute Myeloid Leukemia Clinical Trial

— 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01451268
• Other study ID #: CLBH589 BDE05T
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: September 30, 2011
• Last updated: March 19, 2018
• Start date: January 2011
• Est. completion date: April 2018

Study information

• Verified date: March 2018
• Source: Johann Wolfgang Goethe University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Germany	University Hospital Düsseldorf	Düsseldorf
Germany	University Hospital Essen	Essen
Germany	University Hospital Frankfurt	Frankfurt am Main
Germany	University Hospital Hamburg-Eppendorf	Hamburg
Germany	University Hospital Mainz	Mainz
Germany	University Hospital Marburg	Marburg

Sponsors (1)

Lead Sponsor	Collaborator
Johann Wolfgang Goethe University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of panobinostat		after 28 days of administration
Primary	Dose-limiting toxicity (MTD) of Panobinostat		after 28 days of administration
Secondary	Cumulative incidence of hematologic relapse and death		one year after HSCT
Secondary	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
Secondary	Time to complete donor chimerism		patients will be followed for up to 2 years depending on the duration of study participation
Secondary	Cumulative incidence of extensive chronic GvHD		one year after HSCT
Secondary	Duration of complete donor chimerism		patients will be followed for up to 2 years depending on the duration of study participation
Secondary	Cumulative incidence of severe acute GvHD		one year after HSCT
Secondary	patient-reported health-related quality of life		after 3 months of administration and one month after last intake of study drug

External Links

•   Trial register of University Cancer Center Frankfurt, additional trial information