Clinical trial NCT04669210: PTCy and Ruxolitinib vs PTCy, Tacrolimus and MMF in MUD and Haploidentical HSCT
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2020-12-16
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.
16. Somatic or mental pathology not allowing to sign informed consent.

Primary outcomes:
measure: Incidence of acute GVHD grade II-IV
timeFrame: 125 days
Secondary outcomes:
measure: Non-relapse mortality
timeFrame: 2 years
measure: Relapse incidence
timeFrame: 2 years
measure: Incidence of moderate and severe chronic GVHD
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Event-free survival
timeFrame: 2 years
measure: Incidence of HSCT-associated adverse events (safety and toxicity)
timeFrame: 125 days
measure: Primary or secondary graft failure
timeFrame: 2 years
measure: Incidence of infections
timeFrame: 6 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Hematology Research Center
city: Saint Petersburg
country: Russian Federation
facility: RM Gorbacheva Research Institute
Study officials:
References: