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

Sponsor
St. Petersburg State Pavlov Medical University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04943757
Collaborator
(none)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Graft-versus-host Disease Prophylaxis With Combination of Post-transplantation Benadamustine and Cyclophosphamide in Patients With Refractory Myeloid Malignancies (PTBCy)
Actual Study Start Date :
Jan 21, 2021
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

Arm Intervention/Treatment
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

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

Outcome Measures

Primary Outcome Measures

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

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

Secondary Outcome Measures

  1. - Incidence of Cytokine release syndrome [100 days]

    Proportion of patients with cytokine release syndrome according to ASBMT Consensus Grading for Cytokine Release Syndrome, 2018

  2. Incidence of HSCT-associated adverse events (safety and toxicity) [100 days]

    Toxicity assessment is based on NCI CTC AE 5.0 grades. Veno-occlusive disease incidence and severity assessment is based on EBMT criteria 2016. Transplant-associated microangiopathy incidence assessment is based on Cho et al.

  3. Incidence of acute GVHD grade II-IV [125 days]

    Cumulative incidence of patients with acute GVHD II-IV grade

  4. Incidence of moderate and severe chronic GVHD [1 year]

    Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria

  5. Relapse rate analysis [1 year]

    Cumulative incidence of patients with relapse

  6. Non-relapse mortality analysis [1 year]

    Cumulative incidence of patients with mortality without hematological relapse of malignancy

  7. Overall survival analysis [1 year]

    Kaplan-Meier estimate of death from all causes

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 RM Gorbacheva Research Institute Saint Petersburg Russian Federation 197022

Sponsors and Collaborators

  • St. Petersburg State Pavlov Medical University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ivan S Moiseev, Vice-director for science RM Gorbacheva Institute, St. Petersburg State Pavlov Medical University
ClinicalTrials.gov Identifier:
NCT04943757
Other Study ID Numbers:
  • 05/21-n
First Posted:
Jun 29, 2021
Last Update Posted:
Apr 5, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ivan S Moiseev, Vice-director for science RM Gorbacheva Institute, St. Petersburg State Pavlov Medical University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 5, 2022