Panobinostat Maintenance After HSCT fo High-risk AML and MDS

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Goethe University
• Collaborators: Jan J. Cornelissen (HOVON-SAKK); Sebastian Giebel (PALG)
• Treatments: Panobinostat

Criteria

Inclusion Criteria:

• 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

or

• 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:

1. Matched sibling or matched unrelated donor (i.e. 10/10 or 9/10 HLA-matched) or haploidentical family donor

2. Conditioning regimens:

1. Reduced-intensity conditioning:

a. Fludarabine/Melphalan b. Fludarabine/Busulfan2 (FB2) (2) Myeloablative conditioning:

1. Fludarabine/Busulfan4 (FB4)

2. Busulfan/Cyclophosphamide (BU/CY)

3. Fludarabine/TBI 8 Gy

4. Cyclophosphamide/TBI 12 Gy (3) Fludarabine/Cyclophosphamide/TBI 2 Gy in combination with post-Tx cyclophosphamide (TP-CY) only (4) Thiotepa/Busulfan/Fludarabine (TBF) in the context of an haploidentical HSCT only (5) In case of active disease at HSCT, salvage chemotherapy prior to conditioning is permitted

c. Strategies for GvHD prophylaxis:

1. HLA-matched donors:

a. CSA + MMF +/- ATG b. CSA + MTX +/- ATG c. PT-CY + CSA

2. Haploidentical donors:

d. PT-CY + CSA + MMF

• No history of significant cardiac disease and absence of active symptoms, otherwise documented left ventricular EF ≥ 40%

• Written informed consent for registration

Exclusion Criteria:

• 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