AML, t-MN, MDS, MDS/MPN, CMML-1/CMML-2
Conditions
Interventions
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Trade Name: Grafalon 20 mg/ml
Pharmaceutical Form: Concentrate for solution f
Sponsors
DKMS gemeinnuetzige GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed written Informed Consent and able to understand the nature of the trial and the trial related procedures and to comply with them (see Section 24.3). - Age = 18 years. - One of the following eligible diagnoses: - AML in CR1 with intermediate or adverse risk genetic abnormalities (according to the ELN 2017 guidelines), or undefined risk. - AML of any ELN risk category after hematological or molecular relapse, or with primary refractory disease. - AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN 2017 guidelines) are present. - Therapy-related myeloid neoplasia (t-MN), except if favourable genetic abnormalities (according to ELN 2017 guidelines) are present. - MDS with intermediate risk, high risk or very high risk disease (according to the IPSS-R Score) regardless of treatment status. - MDS/MPN and CMML-1/CMML-2 regardless of treatment status. - Transplantation with Peripheral Blood Stem Cells (PBSC) scheduled to be performed 4 to 14 days after date of randomization. - The left ventricular ejection fraction (LVEF) was assessed =40% at last echocardiography. - The scheduled donor is unrelated to the patient, and matched or partially matched (with not more than one allele or antigen mismatch) at HLA-A, -B, -C, or -DRB1. - Absence of pregnancy confirmed by highly sensitive pregnancy test for WOCBP (see Section 17.6). Test must not date back - more than 3 days prior to randomization, or - more than 3 days prior to start of conditioning, if it started before randomization. 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 540 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 540
Exclusion criteria
Exclusion criteria: - Anamnestic intravenous or subcutaneous exposure to rabbit immunoglobin-preparations (e.g. Grafalon? or Thymoglobulin?) - Known hypersensitivity to ATG-Grafalon or its excipients. - Known hypersensitivity to cyclophosphamide, its metabolites or excipients. - Prior allogeneic hematopoietic transplantation. - Patients who receive supplementary continuous oxygen at the time of randomization. - Symptomatic heart failure (NYHA =2) at the time of randomization. - Uncontrolled viral, bacterial or fungal infection with progression or no clinical improvement at the time of randomization. - Symptomatic cystitis or known obstruction of urine flow at the time of randomization. - Breast-feeding women. - WOCBP and fertile male patients unable or unwilling to follow highly effective contraception methods from enrollment to minimum six months after the last dose of the IMP (see Section 17.6). - Simultaneous participation in another interventional clinical trial with an investigational medicinal product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: One of the key elements to improve allogeneic HCT is the administration of optimized conditioning treatment including immunosuppressive drugs to facilitate engraftment, prevent GVHD and induce tolerance of donor immune cells. Specifically the goal of this trial is: 1. to investigate the impact of PTCY versus ATG-Grafalon as part of a conditioning treatment for alloHCT on overall survival. 2. to investigate the potential of PTCY versus ATG-Grafalon to allow for disease-free and immunosuppression-free survival one year after alloHCT. Information on the investigational drugs provided by these two endpoints will enable the scientific community a comprehensive assessment of the two approaches for alloHCT.;Secondary Objective: Data collected within this trial will further allow: - to assess the risk of acute and chronic GVHD, relapse and NRM after alloHCT per treatment arm - to evaluate risk factors for acute and chronic GVHD, relapse, and NRM. - to test for interactions between the presence or absence of (specific) HLA mismatches and major alloHCT outcomes. - to test for interactions between sex mismatches and major alloHCT outcomes. - to describe organ-specific clinical patterns of GVHD depending on the study arm.;Primary end point(s): overall survival (OS) from time of transplantation (across the whole observational period), and relapse- and immunosuppression-free survival (RIFS) at 1 year from time of transplantation. ;Timepoint(s) of evaluation of this end point: please refer to the combined information given in E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - GVHD- and relapse-free survival (GRFS, events: onset of aGVHD III-IV or cGVHD requiring immunosuppressive treatment, death, relapse). - Event-free survival (EFS, events: relapse and death). - Cumulative incidences of relapse. - Cumulative incidences of non-relapse mortality (NRM). - Cumulative incidences of aGVHD grades II-IV during the first 180 days from HCT. - Cumulative incidences of aGVHD grades III-IV during the first 180 days from HCT. - Cumulative incidences of cGVHD during first 2 years from HCT. - Cumulative incidences of severe cGVHD during the first 2 years from HCT. - Rate of complete remission without measurable residual disease until Day 56 from HCT. - Rate of engraftment failure until Day 56 from HCT. - Rate of patients requiring intensive care (organ replacement therapy) by Day 56 from HCT. - Cumulative incidence of CMV reactivations during first 180 days from HCT. ;Timepoint(s) of evaluation of this end point: please refer to the combined information given in E.5.2. | — |
Countries
Germany
Contacts
Public ContactClinical Trials Unit
DKMS gemeinnuetzige GmbH
Outcome results
None listed