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

Myelodysplastic Syndromes Clinical Trial

— PTBCy  

Official title:

Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04943757
• Other study ID #: 05/21-n
• Status: Recruiting
• Phase: Phase 2
• Start date: January 21, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2022
• Source: St. Petersburg State Pavlov Medical University
• Contact: Ivan S Moiseev, MD, Prof.
• Phone: +79217961951
• Email: moisiv[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myeloid Leukemia, Acute
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm

Intervention

Drug:
• Bendamustine Hydrochloride
50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation
• Cyclophosphamid
25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

Locations

Country	Name	City	State
Russian Federation	RM Gorbacheva Research Institute	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival analysis [ Time Frame: 1 year ]	Measure: Kaplan-Meier estimate of death or relapse, or graft failure	1 year
Secondary	- Incidence of Cytokine release syndrome	Proportion of patients with cytokine release syndrome according to ASBMT Consensus Grading for Cytokine Release Syndrome, 2018	100 days
Secondary	Incidence of HSCT-associated adverse events (safety and toxicity)	Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al.	100 days
Secondary	Incidence of acute GVHD grade II-IV	Cumulative incidence of patients with acute GVHD II-IV grade	125 days
Secondary	Incidence of moderate and severe chronic GVHD	Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria	1 year
Secondary	Relapse rate analysis	Cumulative incidence of patients with relapse	1 year
Secondary	Non-relapse mortality analysis	Cumulative incidence of patients with mortality without hematological relapse of malignancy	1 year
Secondary	Overall survival analysis	Kaplan-Meier estimate of death from all causes	1 year