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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04943757
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	St. Petersburg State Pavlov Medical University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Russian Federation
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myeloid Leukemia, Acute, Chronic Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm

Arms & Interventions

Arms

Experimental: 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

Interventions

Drug: - Bendamustine Hydrochloride

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

Drug: - Cyclophosphamid

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation

Status

Recruiting

Address

RM Gorbacheva Research Institute

Saint Petersburg, , 197022

Site Contact

Ivan Moiseev

[email protected]

+79217961951

Site by: Kaleidoscopic

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