Panobinostat Maintenance After HSCT fo High-risk AML and MDS

NCT04326764 | Terminated Phase 3 DMC

• 1 other identifier: ETAL-4 / HOVON-145
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 19

Brief Summary

Aim of this prospective randomized trial is to compare maintenance treatment with panobinostat interspersed with donor lymphocyte infusions (DLI) versus the standard approach of pre-emptive DLI alone in patients with poor-risk AML/MDS having favorably received an allogeneic HSCT followed by engraftment, donor chimerism and hematopoietic reconstitution.

Conditions

Acute Myeloid Leukaemia (AML); Myelodysplastic Syndromes (MDS)

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  OS is measured from date of randomization to the date of death or date of last follow up. Observations of patients alive at last follow up will be censored at date of last follow up.

  5 years

Secondary Outcomes (10)

• Event-free survival (EFS)

  5 years

• Disease-free survival (DFS)

  5 years

• Cumulative incidence of hematologic relapse

  5 years

• Cumulative incidence, time and cause of non-relapse mortality (NRM)

  5 years

• Cumulative incidence of new onset or aggravation of acute GvHD grade III-IV

  5 years

Study Arms (2)

Panobinostat

EXPERIMENTAL

Panobinostat 20 mg oral three times weekly every second week

Drug: Panobinostat

Standard of Care

NO INTERVENTION

Treatment according to local standards

Interventions

Panobinostat DRUG

Panobinostat should be taken orally once on each scheduled day at about the same time, either with or without food. Each dose of panobinostat should be taken with a cup of water. The capsules should be swallowed as whole. If vomiting occurs during the course of treatment, no re-dosing is allowed before the next scheduled dose. If one dose is forgotten during the morning on a scheduled treatment day then the missed dose should be taken on that same day within 12 hours. After more than 12 hours, that day's dose should be withheld, and the patient should wait to take panobinostat until the next schedule treatment day. The patient should then continue treatment with the original dosing schedule. Panobinostat will be administered at a dose of 20 mg three times weekly (TIW) every second week and will be dosed on a flat scale of mg/day and not by weight or body surface area. Panobinostat will be dispensed as a 20 mg capsule or as two 10 mg capsules.

Also known as: Farydak

Panobinostat

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (18-70 years of age)
• AML (except acute promyelocytic leukemia with PML-RARA and AML with BCR-ABL1) according to WHO 2016 classification 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 14-21 of the first induction cycle
• adverse risk according to ELN 2017 risk stratification by genetics (Appendix 2) regardless of stage
• secondary to MDS or radio-/chemotherapy
• MRD positive before HSCT based on flow cytometry or PCR
• MDS with excess blasts (MDS-EB) according to the WHO 2016 classification, or high-risk or very high-risk according to IPSS-R
• and
• First allogeneic HSCT scheduled within the next 4-6 weeks using one of the following donors, conditioning regimens and strategies for GvHD prophylaxis:
• Matched sibling or matched unrelated donor (i.e. 10/10 or 9/10 HLA-matched) or haploidentical family donor
• Conditioning regimens:
• Reduced-intensity conditioning:
• a. Fludarabine/Melphalan b. Fludarabine/Busulfan2 (FB2) (2) Myeloablative conditioning:
• Fludarabine/Busulfan4 (FB4)

You may not qualify if:

• \- Prior treatment with a DAC inhibitor
• \- Hypersensitivity to the active substance or to any of the excipients of panobinostat
• HIV or HCV antibody positive
• Psychiatric disorder that interferes with ability to understand the study and give informed consent, and/or impacts study participation or follow-up.
• Female patients who are pregnant or breast feeding
• History of another primary malignancy that is currently clinically significant or currently requires active intervention

Sponsors & Collaborators

• Goethe University: lead
• Stichting Hemato-Oncologie voor Volwassenen Nederland: collaborator
• Polish Adult Leukemia Group: collaborator
• Schweizerische Arbeitsgemeinschaft für klinische Krebsforschung: collaborator

Study Sites (19)

Robert Bosch Krankenhaus

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

University Hospital Jena

Jena, Thuringia, 07747, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Thuringia, 04103, Germany

Location

Klinikum Augsburg

Augsburg, Germany

Location

University Hospital Bonn

Bonn, Germany

Location

Universtity Hospital Dresden

Dresden, 01307, Germany

Location

University Hospital Frankfurt

Frankfurt, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, Germany

Location

Otto-von-Guericke University

Magdeburg, 39120, Germany

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Klinikum Mannheim

Mannheim, Germany

Location

Philipps-Universität Marburg

Marburg, Germany

Location

University Hospital Münster

Münster, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, 90419, Germany

Location

Amsterdam University Medical Center - VUMC

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Radboud UMC

Nijmegen, 6500 HB, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015, Netherlands

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

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

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, PD Dr.

  Goethe University Frankfurt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Transplant Program, Principal Investigator

Study Record Dates

• First Submitted: March 21, 2019
• First Posted: March 30, 2020
• Study Start: July 24, 2018
• Primary Completion: February 13, 2023
• Study Completion: February 13, 2023
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

DE (14); NL (5)