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

NCT ID: NCT07238712

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-10
• Study Completion Date: 2026-12-10

Brief Summary

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

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Abatacept (Orencia)

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Abatacept (Orencia)

Intervention Type: DRUG

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

Interventions

Ruxolitinib

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

Intervention Type: DRUG

Abatacept (Orencia)

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ivan S Moiseev

RM Gorbacheva Research Institute Scientific director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Pavlov University

Saint Petersburg, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Alexandr D Kulagin, MD, Prof

Role: CONTACT

bmt-director@1spbgmu.ru

+78123386265

Ivan S Moiseev, MD, Prof.

Role: CONTACT

moisiv@mail.ru

+78123386201

Facility Contacts

Role: primary

moisiv@mail.ru

8123387193

References

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.

Reference Type: BACKGROUND

PMID: 40372957 (View on PubMed)

Other Identifiers

30/25-n

Identifier Type: -

Identifier Source: org_study_id