MedDRA version: 21.0 Level: LLT Classification code 10024349 Term: Leukemia myeloid System Organ Class: 100000004864 MedDRA version: 20.1 Level: LLT Classification code 10024330 Term: Leukemia acute System Organ Class: 100000004864
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
Other descriptive name: CYTARABINE
Pharmaceutical Form: Solution for injection
INN or Proposed INN: MITOXANTRONE HYDROCHLORIDE
CAS Number: 7
Sponsors
DKMS gemeinnützige GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed written informed consent. - Male and female patients of 18 to 75 years of age. - Diagnosis of AML according to WHO criteria. - Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist. - No known history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) =40% (adjusted for hemoglobin, if available) and FEV1/FVC = 50%. - HLA-identical sibling. or - HLA-compatible unrelated donor (=9/10 antigens matched for HLA-A, -B, -C, -DRB1, and –DQB1) with completed confirmatory typing or - Two unrelated donors with >90% probability of 9/10 match for HLA-A, -B, -C, -DRB1, and –DRQB1, according to OptiMatch® list. - Relapse patients: First AML relapse, defined as =5% bone marrow blasts and / or extramedullary AML manifestation. - Poor-responders: with =5% bone marrow blasts after the first cycle of induction therapy, and one of the following subtypes/risk groups of AML: -AML that evolves from previously documented myelodysplastic syndrome (MDS), or after a Myeloproliferative Neoplasia (MPN) or Diagnosis of therapy-related myeloid neoplasm (t-MN)or -Non favourable risk AML according to ELN-criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 108
Exclusion criteria
Exclusion criteria: - Acute promyelocytic leukemia (APL). WBC count of =50 GPt/L at study inclusion. - For poor-responder patients the first cycle of induction therapy contained HDAC, defined as cytarabine at single-doses of >1g/ m2. - Patient has received more than 440 mg/m2 daunorubicin equivalents - Severe organ dysfunction, defined as any of the following: Left ventricular ejection fraction 1.5 x ULN (if not considered Gilbert-Syndrome), or ASAT/ALAT >5 x ULN. Estimated GFR < 50 ml/min. - Treatment with any investigational drug within 10 days before study entry. - Uncontrolled infection at the time of enrollment. - History of allogeneic transplantation. - Manifestation of AML in the central nervous system. - Pregnant or breast-feeding women. - Men unable or unwilling to use adequate contraception methods from start of study treatment to minimum of six months after the last dose of chemotherapy. -Women with childbearing potential except those who fulfill the following criteria: Post-menopausal or post-operative or continuous and correct application of a contraception method with a Pearl Index < 1 % or sexual abstinence or vasectomy of the sexual partner.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this trial is to compare outcome of two treatment strategies for patients with high-risk AML who failed to achieve or maintain a complete remission with standard therapy.;Secondary Objective: Not applicable;Primary end point(s): disease-free survival on day 56 after allogeneic stem cell transplantation. This composite endpoint consists of two major components: i) To have received allogeneic HCT within 16 weeks after randomization and; ii) to be free of disease on 56 days after HCT.;Timepoint(s) of evaluation of this end point: day 56 after HCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival by treatment arm is the most important secondary endpoint. In addition the rate of allogeneic stem cell transplantation, cumulative incidence of CR, and leukemia-free survival will be assessed by treatment arm. ;Timepoint(s) of evaluation of this end point: OS cumulative incidence until min. 2 years after randomization Rate of HCT at 4, 8 and 16 weeks CR cumulative incidence at 4, 8 and 24 weeks. LFS | — |
Countries
Germany
Contacts
Public ContactStudy Manager
DKMS gemeinnützige GmbH
Outcome results
None listed