A Randomized, Multicenter, Open-label Phase II Trial to Compare Prophylaxis of Graft Versus Host Disease With Tacrolimus and Mycophenolate Mofetil Versus Ruxolitinib After Post-transplant Cyclophosphamide
Overview
- Phase
- Phase 2
- Intervention
- Tacrolimus
- Conditions
- Graft-versus-host-disease
- Sponsor
- St. Petersburg State Pavlov Medical University
- Enrollment
- 128
- Locations
- 2
- Primary Endpoint
- Incidence of acute GVHD grade II-IV
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This is multicenter investigator-initiated randomized open-label phase II clinical trial to compare prophylaxis of graft versus host disease treated with tacrolimus and mycophenolate mofetil versus ruxolitinib after post-transplant cyclophosphamide.
In total 128 patients will be included in the study. After inclusion into the study and performing of transplantation patients will be randomized in 1:1 proportion in two arms (64 patients per arm): arm A will include patients who will be treated with cyclophosphamide and ruxolitinib for GVHD prophylaxis; arm B will include patients who will be treated with cyclophosphamide, tacrolimus and MMF for GVHD prophylaxis. After the end of the treatment patients will be followed-up during two years.
Investigators
Ivan S Moiseev
RM Gorbacheva Research institute scientific director
St. Petersburg State Pavlov Medical University
Eligibility Criteria
Inclusion Criteria
- •Informed consent to participate in the study, signed by the patient;
- •Diagnosis: acute lymphoblastic or acute myeloblastic leukemia;
- •Morphological remission, defined as less than 5% of blasts by microscopy or flow cytometry with a peripheral leukocyte level of more than 1.500 μL. It is acceptable to include patients without restored platelets or erythrocytes;
- •Indications for performing allogeneic hematopoietic stem cell transplantation, determined by the participating center in accordance with local medical practice;
- •Unrelated or haploidentical donor;
- •Age 18-70 years;
- •Functional status according to ECOG scale 0-2 score.
Exclusion Criteria
- •Repeated allogeneic transplantation, regardless of the indications for its implementation;
- •Source of graft - umbilical cord stem cells;
- •Any ex vivo modification of the graft with the exception of separation or washing of red blood cells;
- •The presence of more than 5% of clonal tumor cells according to flow cytometry in the presence of morphological remission;
- •Diagnosis: acute promyelocytic leukemia;
- •Severe organ failure: creatinine more than 2 ULN; ALT, AST more than 5 ULN; bilirubin more than 1.5 ULN; respiratory failure more than 1 grade;
- •Unstable hemodynamics, requiring the introduction of vasopressors;
- •Uncontrolled bacterial or fungal infection at the time of randomization, determined by the level of CRP\> 70 mg/l with adequate antibacterial or antifungal therapy;
- •Rhythm disturbances that persist despite adequate antiarrhythmic therapy: a tachysystolic form of atrial fibrillation, ventricular arrhythmias V gradation according to Laun, AV block of III degree;
- •Decrease in ejection fraction according to echocardiography less than 40%;
Arms & Interventions
PTCY tacrolimus MMF
Conditioning: fludarabine 180 mg/m2 busulfan 8-14 mg/kg per os GVHD prophylaxis: cyclophosphamide 50 mg/kg day+3, +4 tacrolimus 0.03 mg/kg from day+5 to 100 mycophenolate mofetil 30 mg/kg from day+5 to 35
Intervention: Tacrolimus
PTCY tacrolimus MMF
Conditioning: fludarabine 180 mg/m2 busulfan 8-14 mg/kg per os GVHD prophylaxis: cyclophosphamide 50 mg/kg day+3, +4 tacrolimus 0.03 mg/kg from day+5 to 100 mycophenolate mofetil 30 mg/kg from day+5 to 35
Intervention: Mycophenolate Mofetil
PTCY ruxolitinib
Conditioning: fludarabine 180 mg/m2 busulfan 8-14 mg/kg per os ruxolitinib 5 mg tid days -7 to -2 GVHD prophylaxis: cyclophosphamide 50 mg/kg day+3, +4 ruxolitinib 5 mg tid days +5 to +21 ruxolitinib 5 mg bid days +22 to +150
Intervention: Ruxolitinib
Outcomes
Primary Outcomes
Incidence of acute GVHD grade II-IV
Time Frame: 125 days
Proportion of patients with acute GVHD II-IV grade
Secondary Outcomes
- Overall survival(2 years)
- Primary or secondary graft failure(2 years)
- Incidence of moderate and severe chronic GVHD(2 years)
- Event-free survival(2 years)
- Non-relapse mortality(2 years)
- Incidence of HSCT-associated adverse events (safety and toxicity)(125 days)
- Incidence of infections(6 months)
- Relapse incidence(2 years)