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

NCT ID: NCT04943757

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-21
• Study Completion Date: 2024-05-30

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.

Conditions

Myeloid Leukemia, Acute; Chronic Myeloid Leukemia; Myelodysplastic Syndromes; Myeloproliferative Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PTBCy graft-versus-host disease prophylaxis

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 +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 3 g/day, iv or po x 30 days; Days +5 through +100: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Group Type: EXPERIMENTAL

Bendamustine Hydrochloride

Intervention Type: DRUG

50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

Cyclophosphamid

Intervention Type: DRUG

25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

Interventions

Bendamustine Hydrochloride

50 mg/m2 iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

Intervention Type: DRUG

Cyclophosphamid

25 mg/kg iv Days +3 through +4 after allogeneic hematopoietic stem cell transplantation

Intervention Type: DRUG

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

• 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

Vice-director for science RM Gorbacheva Institute

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

RM Gorbacheva Research Institute

Saint Petersburg, , Russia

Countries

Russia

References

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.

Reference Type: BACKGROUND

PMID: 33845259 (View on PubMed)

Other Identifiers

05/21-n

Identifier Type: -

Identifier Source: org_study_id