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

Acute Myeloid Leukemia Clinical Trial

— PTCyRuxo  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04669210
• Other study ID #: CINC424ARU01T
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 3, 2020
• Est. completion date: February 2025

Study information

• Verified date: April 2023
• Source: St. Petersburg State Pavlov Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 128
• Est. completion date: February 2025
• Est. primary completion date: February 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoid Leukemia
• Acute Myeloid Leukemia
• Graft vs Host Disease
• Graft-versus-host-disease
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Stem Cell Transplant Complications

Intervention

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.
• Tacrolimus
Tacrolimus 0.03 mg/kg adjusted to concentrations 5-15 ng/ml from day+5 to +100
• Mycophenolate Mofetil
Mycophenolate mofetil 30 mg/kg from day +5 to +35

Locations

Country	Name	City	State
Russian Federation	National Hematology Research Center	Moscow
Russian Federation	RM Gorbacheva Research Institute	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of acute GVHD grade II-IV	Proportion of patients with acute GVHD II-IV grade	125 days
Secondary	Non-relapse mortality	Cumulative incidence of patients with mortality without hematological relapse of malignancy	2 years
Secondary	Relapse incidence	Cumulative incidence of patients with relapse	2 years
Secondary	Incidence of moderate and severe chronic GVHD	Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria	2 years
Secondary	Overall survival	Kaplan-Meier estimate of death from all causes	2 years
Secondary	Event-free survival	Kaplan-Meier estimate of death or relapse	2 years
Secondary	Incidence of HSCT-associated adverse events (safety and toxicity)	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.	125 days
Secondary	Primary or secondary graft failure	Cumulative incidence of patients with primary or secondary graft failure defined by the absence of donor chimerism.	2 years
Secondary	Incidence of infections	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	6 months