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

NCT04943757 | Completed Phase 2

• 1 other identifier: 05/21-n
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Keywords

Bendamustine; Cyclophosphamide; Graft-versus-host disease; Graft-versus-leukemia effect; Refractory; Acute Myeloid leukemia; Hematopoietic Stem Cell Transplantation; Allogeneic

Outcome Measures

Primary Outcomes (1)

• Event-free survival analysis [ Time Frame: 1 year ]

  Measure: Kaplan-Meier estimate of death or relapse, or graft failure

  1 year

Secondary Outcomes (7)

• - Incidence of Cytokine release syndrome

  100 days

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

  100 days

• Incidence of acute GVHD grade II-IV

  125 days

• Incidence of moderate and severe chronic GVHD

  1 year

• Relapse rate analysis

  1 year

Study Arms (1)

PTBCy graft-versus-host disease prophylaxis

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 +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

Drug: Bendamustine Hydrochloride; Drug: Cyclophosphamid

Interventions

Bendamustine Hydrochloride DRUG

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

PTBCy graft-versus-host disease prophylaxis

Cyclophosphamid DRUG

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

PTBCy graft-versus-host disease prophylaxis

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

Location

Related 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.

  PMID: 33845259 BACKGROUND

MeSH Terms

Conditions

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

Interventions

Bendamustine Hydrochloride; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science RM Gorbacheva Institute

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 29, 2021
• Study Start: January 21, 2021
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

RU (1)