PTCyRuxo: PTCy and Ruxolitinib vs PTCy, Tacrolimus and MMF in MUD and Haploidentical HSCT

St. Petersburg State Pavlov Medical University (Other)
Overall Status
Recruiting ID

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Anticipated Enrollment :
128 participants
Intervention Model:
Parallel Assignment
None (Open Label)
Primary Purpose:
Official Title:
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
Actual Study Start Date :
Nov 3, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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

Drug: Tacrolimus
Tacrolimus 0.03 mg/kg adjusted to concentrations 5-15 ng/ml from day+5 to +100
Other Names:
  • Prograf
  • Drug: Mycophenolate Mofetil
    Mycophenolate mofetil 30 mg/kg from day +5 to +35
    Other Names:
  • CellCept
  • Experimental: 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

    Drug: Ruxolitinib
    Ruxolitinib administered during conditioning 5 mg tid before allogeneic hematopoietic stem cell transplantation, 5 mg tid days 5-21 and 5 mg bid days 22-150 after transplantation instead of tacrolimus and MMF.
    Other Names:
  • Jakavi
  • Outcome Measures

    Primary Outcome Measures

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

      Proportion of patients with acute GVHD II-IV grade

    Secondary Outcome Measures

    1. Non-relapse mortality [2 years]

      Cumulative incidence of patients with mortality without hematological relapse of malignancy

    2. Relapse incidence [2 years]

      Cumulative incidence of patients with relapse

    3. Incidence of moderate and severe chronic GVHD [2 years]

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

    4. Overall survival [2 years]

      Kaplan-Meier estimate of death from all causes

    5. Event-free survival [2 years]

      Kaplan-Meier estimate of death or relapse

    6. Incidence of HSCT-associated adverse events (safety and toxicity) [125 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. criteria. All toxicity measurements will be aggregated as severity scores.

    7. Primary or secondary graft failure [2 years]

      Cumulative incidence of patients with primary or secondary graft failure defined by the absence of donor chimerism.

    8. Incidence of infections [6 months]

      Number of patients with bacteremia before engraftment, bacteremia after engraftment, severe sepsis (presence of multiple organ failure), pneumonia, soft tissue infection, invasive mycosis (probable or proven invasive aspergillosis, candidaemia, zygomycosis), reactivation of cytomegalovirus, other opportunistic viral infections

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    1. Informed consent to participate in the study, signed by the patient;

    2. Diagnosis: acute lymphoblastic or acute myeloblastic leukemia;

    3. 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;

    4. Indications for performing allogeneic hematopoietic stem cell transplantation, determined by the participating center in accordance with local medical practice;

    5. Unrelated or haploidentical donor;

    6. Age 18-70 years;

    7. Functional status according to ECOG scale 0-2 score.

    Exclusion Criteria:
    1. Repeated allogeneic transplantation, regardless of the indications for its implementation;

    2. Source of graft - umbilical cord stem cells;

    3. Any ex vivo modification of the graft with the exception of separation or washing of red blood cells;

    4. The presence of more than 5% of clonal tumor cells according to flow cytometry in the presence of morphological remission;

    5. Diagnosis: acute promyelocytic leukemia;

    6. 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;

    7. Unstable hemodynamics, requiring the introduction of vasopressors;

    8. 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;

    9. 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;

    10. Decrease in ejection fraction according to echocardiography less than 40%;

    11. Angina of more than II functional class or unstable angina;

    12. Another severe concomitant pathology, which according to the attending physician does not allow the patient to be included in the study;

    13. Pulmonary pathology with a decrease in FEV1 of less than 60% or pulmonary diffusion capacity of less than 60%;

    14. Inability to quit smoking for up to 6 months after transplantation;

    15. Pregnancy or refusal to perform highly effective contraception for 6 months after transplantation.

    Highly effective contraceptive methods include:
    • Total abstinence: if it corresponds to the preferred and customary way of life of the patient. Periodic abstinence (for example, calendar, ovulation, symptothermal, postovulation methods) and interrupted sexual intercourse are not considered acceptable methods of contraception;

    • Female sterilization (surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before the start of the therapy being studied. In the case of ovariectomy only, the reproductive status of the woman must be confirmed using a subsequent analysis of hormones;

    • Sterilization of the male partner (at least 6 months before screening). For women participating in the study, the sexual partner after a vasectomy should be the only partner;

    • Use of oral, injectable or implanted hormonal contraceptive drugs, intrauterine devices or contraceptive systems, or other forms of hormonal contraception with similar efficacy (failure rate less than 1%), for example, hormonal vaginal rings or transdermal hormonal contraceptives.

    1. Somatic or mental pathology not allowing to sign informed consent.

    Contacts and Locations


    Site City State Country Postal Code
    1 National Hematology Research Center Moscow Russian Federation 125167
    2 RM Gorbacheva Research Institute Saint Petersburg Russian Federation 197022

    Sponsors and Collaborators

    • St. Petersburg State Pavlov Medical University


    None specified.

    Study Documents (Full-Text)

    More Information


    None provided.
    Responsible Party:
    Ivan S Moiseev, RM Gorbacheva Research institute scientific director, St. Petersburg State Pavlov Medical University Identifier:
    Other Study ID Numbers:
    • CINC424ARU01T
    First Posted:
    Dec 16, 2020
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by Ivan S Moiseev, RM Gorbacheva Research institute scientific director, St. Petersburg State Pavlov Medical University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 5, 2022