Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Prognosis of patients undergoing salvage allogeneic stem cell transplantation for refractory leukemia or other refractory myeloid malignanies is poor. 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. On the other hand post-transplantation cyclophocphamide was reported to abort cytokine release syndrome that sometimes occurs after graft transfusion in patients after haploidentical graft transfusion. The aim of this study is to evaluate if the combination of post-transplantation 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Petersburg State Pavlov Medical University
• Treatments: Bendamustine Hydrochloride; Cyclophosphamide

Criteria

Inclusion Criteria:

• Patients with indication for allogeneic hematopoietic stem cell transplantation

• Patients with 5-10/10 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

• Salvage hematopoietic stem cell transplantation defined as:

• Acute myeloid leukemia: >5% of clonal blasts despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: >10% of blasts despite previous therapy with -7 or complex karyotype, or p53 mutation Chronic myeloid leukemia: blast crisis or acceleration phase despite at least 3 previous lines of TKIs Myeloprolipherative neoplasms : high tumor burden despite previous therapy, including >20 000 WBC/ ul or splenomegaly >15 cm

• No severe concurrent illness

Exclusion Criteria:

• Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%

• Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted

• Respiratory distress >grade I

• Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits

• Creatinine clearance < 60 mL/min

• Uncontrolled bacterial or fungal infection at the time of enrollment

• Requirement for vasopressor support at the time of enrollment

• Karnofsky index <30%

• Pregnancy

• Somatic or psychiatric disorder making the patient unable to sign informed consent