Optimization of Post-transplantation Benadamustine and Cyclophosphamide in Patients With High-risk Myeloid Malignancies and a Partially Mismatched Donor (APTBCy)

Optimization of Post-transplantation Benadamustine and Cyclophosphamide in Patients With High-risk Myeloid Malignancies and a Partially Mismatched Donor (APTBCy)

Optimization of bendamustine-containg graft-versus-host disease (GVHD) prophylaxis to reduce the incidence of secondary haemophagocytic lymphohistiocytosis and GVHD

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia; Myelodysplastic Syndromes (MDS); Acute Myeloid Leukemia (AML); Atypical Chronic Myeloid Leukemia; Myeloprolipherative Neoplsm
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Abatacept (Orencia)

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexandr D Kulagin, MD, Prof; Phone Number: +78123386265; Email: bmt-director@1spbgmu.ru
• Study Contact Backup: Name: Ivan S Moiseev, MD, Prof.; Phone Number: +78123386201; Email: moisiv@mail.ru

Study Locations

• Russia
  • Saint Petersburg, Russia, 197022
    • Recruiting
    • Pavlov University
    • Contact: Phone Number: 8123387193; Email: moisiv@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Test cohort 1 - ruxolitinib; Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.; mycophenolate mofetil Days +5 through +35 30 mg/kg/day p.o.; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration	Drug: Ruxolitinib; ; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.
Experimental: Test cohort 2 - abatacept; Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.; mycophenolate mofetil Days +5 through +35 30 mg/kg/day p.o.; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration	Drug: Abatacept (Orencia); Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.
Experimental: Experimental: Expansion cohort; Days +3 through +4: Bendamustine 50 mg/m2 iv x 2 days; Days +3 through +4: Cyclophosphamide 25 mg/kg iv x 2 days; Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration	Drug: Abatacept (Orencia); Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival analysis	Measure: Kaplan-Meier estimate of death from all causes	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-relapse mortality analysis	Cumulative incidence of patients with mortality without hematological relapse of malignancy	2 years
Incidence of secondary hemophagocytic lymphohistiocytosis	Based on H-score diagnostic criteria.	100 days
Incidence of HSCT-associated adverse events (safety and toxicity)	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.	100 days
Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence	Proportion of patients, requiring systemic treatment for bacterial, viral and fungal disease	100 days
Incidence of acute GVHD grade II-IV	Cumulative incidence of patients with acute GVHD II-IV grade	180 days
Incidence of moderate and severe chronic GVHD	Cumulative incidence of patients with moderate and severe chronic GVHD according to MAGIC 2018 criteria	2 years
Relapse rate analysis	Cumulative incidence of patients with relapse	2 years
Event-free survival analysis	Kaplan-Meier estimate of death or relapse	2 years
GVHD-event-free survival analysis	Kaplan-Meier estimate of death, grade III-IV acute GVHD, severe chronic GVHD or relapse	2 years

Collaborators and Investigators

• Sponsor: St. Petersburg State Pavlov Medical University

Publications and helpful links

General Publications

• Moiseev I, Bondarenko S, Vlasova Y, Morozova E, Smirnova A, Epifanovskaya O, Zhogolev D, Chernishova D, Meliboev A, Khudayberdiev J, Mazing A, Lapin S, Kholopova I, Botina A, Baykov V, Popova M, Kosarev O, Kulagin A. Allogeneic hematopoietic cell transplantation with a combination of posttransplantation bendamustine and cyclophosphamide in refractory myeloid neoplasms. Cancer. 2025 May 15;131(10):e35893. doi: 10.1002/cncr.35893.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2025
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): December 10, 2026

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: abatacept; ruxolitinib; graft-versus-host disease; Post-transplantation cyclophosphamide; Post-transplantation bendamustine
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Graft vs Host Disease; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Immunoconjugates; Amino Acids, Peptides, and Proteins; Proteins; Antibodies; Immunoglobulins; Blood Proteins; Serum Globulins; Globulins; Abatacept; ruxolitinib
• Other Study ID Numbers: 30/25-n

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 10 years
• IPD Sharing Access Criteria: Submit a study proposal and request to use the data to Pavlov University Clinical Trial department: spbgmutrials@yandex.ru
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No