Clinical trial NCT04943757: Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies
Official title: Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myeloid Leukemia, Acute
Chronic Myeloid Leukemia
Myelodysplastic Syndromes
Myeloproliferative Neoplasm
Keywords: Bendamustine
Cyclophosphamide
Graft-versus-host disease
Graft-versus-leukemia effect
Refractory
Acute Myeloid leukemia
Hematopoietic Stem Cell Transplantation
Allogeneic
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2021-06-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Event-free survival analysis [ Time Frame: 1 year ]
timeFrame: 1 year
Secondary outcomes:
measure: - Incidence of Cytokine release syndrome
timeFrame: 100 days
measure: Incidence of HSCT-associated adverse events (safety and toxicity)
timeFrame: 100 days
measure: Incidence of acute GVHD grade II-IV
timeFrame: 125 days
measure: Incidence of moderate and severe chronic GVHD
timeFrame: 1 year
measure: Relapse rate analysis
timeFrame: 1 year
measure: Non-relapse mortality analysis
timeFrame: 1 year
measure: Overall survival analysis
timeFrame: 1 year
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: RM Gorbacheva Research Institute
Study officials:
References:
citation: Moiseev I, Bondarenko S, Morozova E, Vlasova Y, Dotsenko A, Epifanovskaya O, Babenko E, Botina A, Baykov V, Surkova E, Lapin S, Beynarovich A, Borzenkova E, Golosgchapov O, Kanunnikov M, Kudyasheva O, Ovechkina V, Pirogova O, Porunova V, Rudakova T, Smikova O, Smirnova A, Afansyev B. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study. Transplant Cell Ther. 2021 Jul;27(7):601.e1-601.e7. doi: 10.1016/j.jtct.2021.03.032. Epub 2021 May 7.