Acute Myeloid Leukemia (AML), Atypical Chronic Myeloid Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndromes (MDS), Myeloprolipherative Neoplsm
Conditions
Keywords
Post-transplantation cyclophosphamide, Post-transplantation bendamustine, graft-versus-host disease, abatacept, ruxolitinib
Brief summary
Optimization of bendamustine-containg graft-versus-host disease (GVHD) prophylaxis to reduce the incidence of secondary haemophagocytic lymphohistiocytosis and GVHD
Detailed description
Prognosis of patients undergoing allogeneic stem cell transplantation (HCT) for high-risk myeloid malignancies, including refractory acute myeloid leukemia, with standard HCT technologies have relatively poor prognosis with 10-30% long-term disease-free survival. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. The combination bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.
Interventions
DRUGRuxolitinib
; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.
Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.
Sponsors
St. Petersburg State Pavlov Medical University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with indication for allogeneic hematopoietic stem cell transplantation * Patients with \<10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. * Peripheral blood stem cells or bone marrow as a graft source * Diagnosis: Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms - High-risk disease defined as: Acute myeloid leukemia: \>5% of clonal blasts in bone marrow despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: \>5% of blasts despite previous therapy Myeloid malignancy with with -7 or complex karyotype, or p53 mutation regardless of blast count in bone marrow Treatment-related myelodysplastic syndrome Second or subsequent allogeneic HCT after relapse of a myeloid malignancy Chronic myelomonocytic leukemia Myeloprolipherative neoplasms, unclassifiable \- No severe concurrent illness
Exclusion criteria
* Patients with indication for allogeneic hematopoietic stem cell transplantation * Patients with \<10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. * Peripheral blood stem cells or bone marrow as a graft source * Diagnosis: Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms - High-risk disease defined as: Acute myeloid leukemia: \>5% of clonal blasts in bone marrow despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: \>5% of blasts despite previous therapy Myeloid malignancy with with -7 or complex karyotype, or p53 mutation regardless of blast count in bone marrow Treatment-related myelodysplastic syndrome Second or subsequent allogeneic HCT after relapse of a myeloid malignancy Chronic myelomonocytic leukemia Myeloprolipherative neoplasms, unclassifiable \- No severe concurrent illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival analysis | 2 years | Measure: Kaplan-Meier estimate of death from all causes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of HSCT-associated adverse events (safety and toxicity) | 100 days | Toxicity assessment is based on NCI CTC AE 6.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Schoettler et al. criteria. All toxicity measurements will be aggregated as severity scores. |
| Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence | 100 days | Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease |
| Incidence of acute GVHD grade II-IV | 180 days | Cumulative incidence of patients with acute GVHD II-IV grade |
| Incidence of moderate and severe chronic GVHD | 2 years | Cumulative incidence of patients with moderate and severe chronic GVHD according to MAGIC 2018 criteria |
| Incidence of secondary hemophagocytic lymphohistiocytosis | 100 days | Based on H-score diagnostic criteria. |
| Relapse rate analysis | 2 years | Cumulative incidence of patients with relapse |
| Event-free survival analysis | 2 years | Kaplan-Meier estimate of death or relapse |
| GVHD-event-free survival analysis | 2 years | Kaplan-Meier estimate of death, grade III-IV acute GVHD, severe chronic GVHD or relapse |
| Non-relapse mortality analysis | 2 years | Cumulative incidence of patients with mortality without hematological relapse of malignancy |
Countries
Russia
Contacts
Primary ContactAlexandr D Kulagin, MD, Prof
Backup ContactIvan S Moiseev, MD, Prof.
Outcome results
None listed