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

NCT04669210 | Completed Phase 2 DMC

• 1 other identifier: CINC424ARU01T
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 2

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.

Conditions

Graft-versus-host-disease; Stem Cell Transplant Complications; Acute Myeloid Leukemia; Acute Lymphoid Leukemia

Keywords

Graft-versus-host-disease; Prophylaxis; ruxolitinib; tacrolimus; MMF; PTCY; cyclophosphamide; unrelated donor; haploidentical donor; randomized trial

Outcome Measures

Primary Outcomes (1)

• Incidence of acute GVHD grade II-IV

  Proportion of patients with acute GVHD II-IV grade

  125 days

Secondary Outcomes (8)

• Non-relapse mortality

  2 years

• Relapse incidence

  2 years

• Incidence of moderate and severe chronic GVHD

  2 years

• Overall survival

  2 years

• Event-free survival

  2 years

Study Arms (2)

PTCY tacrolimus MMF

ACTIVE COMPARATOR

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; Drug: Mycophenolate Mofetil

PTCY ruxolitinib

EXPERIMENTAL

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

Interventions

Ruxolitinib DRUG

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.

Also known as: Jakavi

PTCY ruxolitinib

Tacrolimus DRUG

Tacrolimus 0.03 mg/kg adjusted to concentrations 5-15 ng/ml from day+5 to +100

Also known as: Prograf

PTCY tacrolimus MMF

Mycophenolate Mofetil DRUG

Mycophenolate mofetil 30 mg/kg from day +5 to +35

Also known as: CellCept

PTCY tacrolimus MMF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%;
• Angina of more than II functional class or unstable angina;
• Another severe concomitant pathology, which according to the attending physician does not allow the patient to be included in the study;
• Pulmonary pathology with a decrease in FEV1 of less than 60% or pulmonary diffusion capacity of less than 60%;
• Inability to quit smoking for up to 6 months after transplantation;
• Pregnancy or refusal to perform highly effective contraception for 6 months after transplantation.

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (2)

National Hematology Research Center

Moscow, 125167, Russia

Location

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

Location

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ruxolitinib; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Immune System Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: RM Gorbacheva Research institute scientific director

Study Record Dates

• First Submitted: November 26, 2020
• First Posted: December 16, 2020
• Study Start: November 3, 2020
• Primary Completion: February 27, 2023
• Study Completion: March 28, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Access Criteria: Per request to the Ethical Committee of Pavlov University with the study plan and rationale for the use of the data.

Locations

RU (2)