HOVON HO148 AML
- HO148 AML
- Working group party:
- SCT & Supportive care
- 2de lijn
- Level A
- Included patients:
- Active sites:
A phase I/II feasibility study of the combination of panobinostat and midostaurin in recipients of allogeneic stem cell transplantation with Flt3-ITD AML.
please note: No need to send in MRD samples to central lab anymore due to early closure.
12-03-2020: The HO148 is closed for inclusion of patients.
- Prospective Phase I/II study
- Monitoring Type:
- Not any more
- 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.
- 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
- 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
Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center by one of the following options:
- By ALEA; Use goto eCRF button > select the [Patient tab] and click the [Add new patient] button. Complete all items and click the [Submit] button
- By faxing the completed registration/randomization CRF +31 (0)10 704 1028 Monday through Friday, from 09:00 to 17:00 CET
- By phone +31 (0)10 704 1560 Monday through Friday, from 09:00 to 17:00 CET
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