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A phase II study of posttransplantation cyclophosphamide in patients undergoing HLA 6-8/8 match transplantation (JSCT PTCY19)

A phase II study of posttransplantation cyclophosphamide in patients undergoing HLA 6-8/8 match transplantation (JSCT PTCY19)

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Sex (Male / Female):28 / 15 Age (median years (range)):45 (20 - 65) Disease:AML 14/ALL 11/MDS 8/ML 10 Refined disease risk index:Low/intermediate 32/High/very high 11 Hematopoietic cell transplantation (HCT)-specific comorbidity index: 0-2 34/>=3 9 Donor:HLA-matched related donor 10/HLA-matched unrelated donor 11/HLA-mismatchedrelated donor 4/HLA-mismatched unrelated donor 18

On February 4th, 2020, the Hokkaido University Clinical Research Review Committee, an accredited clinical research review board, approved ten sites to conduct the study. The principal investigator subsequently obtained permission from the facility administrators, submitted the implementation plan to the Minister of Health, Labour and Welfare, and the study was listed in the application and information disclosure system of the Japan Clinical Research Review Committee (jRCT) on February 20th, 2020. The study was subsequently initiated, with eight facilities participating in the study. The first case was enrolled in March 2020, and enrollment was terminated on July 5th, 2021, when the target number of 44 cases was reached. 43 of the 44 cases, excluding one ineligible case, were treated in the study.

The serious adverse events reported in this study were death on day 10 post-transplant associated with ventricular tachycardia within 100 days post-transplant, death on day 42 post-transplant associated with sinusoidal obstruction syndrome, and death on day 77 post-transplant resulting from pneumonia progressing to Acute Respiratory Distress Syndrome in three patients, all of which were appropriately reported to the Certified Clinical Research Review Board. The following are the results. Adverse events of grade 3 or higher within 30 days post-transplant included cardiac dysfunction in 2 patients (5%), liver dysfunction in 1 patient (2%), cystitis in 2 patients (5%), oral mucositis in 1 patient (2%), pulmonary dysfunction in 1 patient (2%), a bacterial infection in 8 patients (19%), and febrile neutropenia in 23 patients (53%). Adverse events of grade 3 or higher from 30 to 100 days post-transplant included cardiac dysfunction in 1 case (2%), liver dysfunction in 1 case (2%), cystitis in 1 case (2%), pulmonary dysfunction in 2 cases (5%), viral infection in 1 case (2%), a bacterial infection in 3 cases (7%), and febrile neutropenia in 13 cases (32%).

The incidence of acute Graft-versus-Host Disease (GVHD) of degree III-IV within 100 days post-transplant, the primary endpoint, was 2.3% (95% CI, 0-10%) (threshold 18%). Neutrophil engraftment was observed in 98% of cases, with a median engraftment period of 15 days (range: 13-43 days). At 100 days post-transplant, 16.3% had grade II-IV acute GVHD, 11.6% had all grades of chronic GVHD, and 4.7% had moderate to severe chronic GVHD. At 2 years post-transplant, 14.0% had all grades of chronic GVHD, and 4.7% had moderate to severe chronic GVHD. Overall survival at 1 year was 86.0%, disease-free survival was 76.7%, and non-relapse mortality was 7.0%. At 2 years, overall survival was 75.3%, disease-free survival was 74.0%, and non-relapse mortality was 7.0%.

The primary endpoint of the study, the incidence of acute Graft-versus-Host Disease (GVHD) of grade III-IV within 100 days post-transplant, was met according to the predefined threshold. The secondary endpoints, including the incidence of acute GVHD, chronic GVHD, overall survival, disease-free survival, and recurrence-free mortality, were also favorable. These findings suggest that the use of post-transplant cyclophosphamide as prophylaxis in allogeneic peripheral blood stem cell transplantation for HLA-ma

Feb. 15, 2023

Oct. 13, 2023

No

No shared plan

https://jrct.mhlw.go.jp/latest-detail/jRCTs011190009

Sugita Junichi

Sapporo Hokuyu Hospital

6-6-5-1 Higashisapporo, Shiroishi-ku,Sapporo-shi, Hokkaido

sugitaj@med.hokudai.ac.jp

Sugita Junichi

Sapporo Hokuyu Hospital

6-6-5-1 Higashisapporo, Shiroishi-ku,Sapporo-shi, Hokkaido

+81-11-865-0111

sugitaj@med.hokudai.ac.jp

Complete

Feb. 20, 2020

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1.Patients who have hematologic malignancies as defined at least one of the following:
a) Acute Leukemia: CR
b) Myelodysplastic syndrome: intermediate-II, high as defined by IPSS, or high, very high as defined by WPSS
c) Lymphoma: CR or chemosensitive PR
2.Age: 20-65 years old.
3.Patients who have HLA 6-8/8 matched related or unrelated peripheral blood stem cell donor
4.Performance status: 0-2
5.Patients with adequate physical function (Cardiac, Hepatic, Renal, Pulmonary).
6.Patients who give written informed consent to participate in the study.

1. Patients with active other malignancies or patients with a history of malignancies within 5 years
2. Patients with active infectious disease.
3. Women who are pregnant or lactating
4. Patients who experienced serious hypersensitivity or anaphylaxis to cyclophosphamide, tacrolimus, mycophenolate mofetil.
5. Patients who have positive anti-donor HLA antibody.
6. Patients who are not eligible for this study at the discretion of the investigator.

Both

hematologic malignancies

Peripheral blood stem cell transplantation:infusion of peripheral blood stem cells
GVHD prophylaxis:
Cyclophosphamide 50mg/kg day 3,4
Tacrolimus 0.02-0.03mg/kg day 5-180
Mycophenolate Mofetil 15m/kg x 3 day 5-28

The incidence of grade III-IV acute GVHD at 100 days

1. Engraftment at 100 days.
2. The incidence of acute GVHD and chronic GVHD at 100 days, 1 year, and 2 years.
3. Non-relapse mortality at 100 days, 1 year, and 2 years.
4. The incidence of relapse at 100 days, 1 year, and 2 years.
5. Disease-free survival at 100 days, 1 year, and 2 years.
6. Overall survival at 100 days, 1 year, and 2 years.
7. The incidence of infectious event at 100 days, 1 year, and 2 years.
8. GVHD free, relapse free survival (GRFS) at 100 days, 1 year, and 2 years.
9. The proportion of patients who stopped immunosuppressive drugs within 1 year and 2 year.
10. Noninfectious fever within 7 days after transplantation
11. Grade 3-4 non-hematologic toxicity within 100 days.
12 Subgroup analysis subgroup analysis according to conditioning regimen
13. Subgroup analysis subgroup analysis according to disease risk index (DRI)

+81-11-706-7934

Feb. 04, 2020

none