Main info

Identifier:

HO148 AML

Sponsor:

HOVON

Working group party:

SCT & Supportive care

Age:

18-70

Stage:

2nd Line

Echelon:

Level A

Included patients:

12

(of 40)

Active sites:

5

(of 10)

Title:

A phase I/II feasibility study of the combination of panobinostat and midostaurin in recipients of allogeneic stem cell transplantation with Flt3-ITD AML.

Timeline

News

Flow

Details

Phase:

Prospective Phase I/II study

Monitoring Type:

Not any more

Objectives:

Primary objective:

• To assess the safety and feasibility of post-transplant panobinostat combined with midostaurin in patients with adverse risk AML/RAEB with FLT3-ITD with high allelic ratio in terms of dose limiting toxicity.

Secondary objectives:

• To assess feasibility in terms of completion of the protocol treatment
• To assess efficacy in terms of:
  • Complete hematological remission (with full peripheral blood recovery) rate at 3, 6 and 12 months post alloHSCT.
  • Immunological remission (residual disease assessed by multicolor flowcytometry) at 6 months post alloHSCT
  • Relapse/progression rate as assessed after cycle 1, 3, 5 and 7 and at 12 months post alloHSCT, or at approx. 3, 6 and 12 months post alloHSCT in case of early termination of protocol treatment.
  • Overall survival (OS) from alloHSCT
  • Progression free survival (PFS) from alloHSCT with relapse (for patients in CR) and progression (for patients in PR) and death from any cause as events
  • Engraftment and chimerism at 3, 6 and 12 months post alloHSCT
• To assess toxicity in terms of:
  • The incidence and nature of (serious) adverse events
  • The incidence and severity of acute and chronic GvHD up to 12 months post alloHSCT
  • NRM up to 12 months post alloHSCT
  • Number and percentage of registered patients starting protocol treatment
  • Number and percentage of patients receiving post-transplant epigenetic therapy after alloHSCT

Eligibility

Inclusion Criteria:

• Adult patients (18-70 years of age)
• AML (except acute promyelocytic leukemia, AML M3 and bcr/abl positive AML) according to WHO 2016 classification (Appendix A) or RAEB with IPSS-R ≥ 1.5 with high mutant to wild-type allelic ratio of FltFLT3-ITD
• First allogeneic HSCT scheduled within the next 2 months upon having achieved hematological remission (< 5% blasts at the bone marrow level)
• Matched sibling or matched unrelated donor (i.e. 10/10 or 9/10 HLA-matched) or haploidentical donor
• Using one of the following conditioning regimens:
  • Fludarabine/Cyclophosphamide/TBI 2 Gy in combination with post-Tx cyclophosphamide (TPT-CY) only
  • Fludarabine/Busulfan or Melphalan/Fludarabine/TBI or fludarabin/TBI 8 Gy with post-transplant cyclophosphamide.
• Strategies for GvHD prophylaxis:
  • HLA-matched donors:
  • PT-CY + CSA
• Haploidentical donors:
  • PT-CY + CSA + MMF
• No history of significant cardiac disease and absence of active symptoms, otherwise documented left ventricular EF > 40%
• Negative serum pregnancy test for female patients of childbearing potential, at registration
• Female patients of childbearing potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
• Written informed consent

Exclusion Criteria:

• Known HIV or HCV positivity
• History of active malignancy during the past 2 years with the exception of basal carcinoma of the skin or carcinoma “in situ” of the cervix or breast
• Pregnant or breast-feeding female patients

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals