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

NCT07238712 | Recruiting Phase 2 DMC

• 1 other identifier: 30/25-n
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia; Myelodysplastic Syndromes (MDS); Myeloprolipherative Neoplsm; Atypical Chronic Myeloid Leukemia

Keywords

Post-transplantation cyclophosphamide; Post-transplantation bendamustine; graft-versus-host disease; abatacept; ruxolitinib

Outcome Measures

Primary Outcomes (1)

• Overall survival analysis

  Measure: Kaplan-Meier estimate of death from all causes

  2 years

Secondary Outcomes (9)

• Incidence of secondary hemophagocytic lymphohistiocytosis

  100 days

• Incidence of HSCT-associated adverse events (safety and toxicity)

  100 days

• Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence

  100 days

• Incidence of acute GVHD grade II-IV

  180 days

• Incidence of moderate and severe chronic GVHD

  2 years

Study Arms (3)

Experimental: Test cohort 1 - ruxolitinib

EXPERIMENTAL

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

Test cohort 2 - abatacept

EXPERIMENTAL

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)

Experimental: Expansion cohort

EXPERIMENTAL

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)

Interventions

Ruxolitinib DRUG

; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.

Experimental: Test cohort 1 - ruxolitinib

Abatacept (Orencia) DRUG

Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.

Experimental: Expansion cohort; Test cohort 2 - abatacept

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

Pavlov University

Saint Petersburg, 197022, Russia

RECRUITING

Related Publications (1)

• 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.

  PMID: 40372957 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Graft vs Host Disease

Interventions

ruxolitinib; Abatacept

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Central Study Contacts

Alexandr D Kulagin, MD, Prof

CONTACT

+78123386265; bmt-director@1spbgmu.ru

Ivan S Moiseev, MD, Prof.

CONTACT

+78123386201; moisiv@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: RM Gorbacheva Research Institute Scientific director

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 20, 2025
• Study Start: May 10, 2025
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): December 10, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 10 years
• Access Criteria: Submit a study proposal and request to use the data to Pavlov University Clinical Trial department: spbgmutrials@yandex.ru

Locations

RU (1)