HLA-mismatched unrelated HCT using PTCy

JRCT ID: jRCTs051220057

Registered date:28/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hematologic malignancy
• Date of first enrollment: 28/06/2022
• Target sample size: 29
• Study type: Interventional

Intervention(s)

1) Allogenic hematopoietic cell transplantation from a HLA 1 or 2 allele-mismatched unrelated donor
2) GVHD prophylaxis: Cyclophosphamide (50 mg/kg) is given on day 3, 4 after the graft infusion. Co
ntinuous intravenous tacrolimus (0.03mg/kg/day) and oral mycophenolate mofetil 3000mg/day are i
nitiated from day 5 after transplantation.

Outcome(s)

• Primary Outcome: Grade III-IV acute GVHD-free survival at day 100 after transplantation

Secondary Outcome

1) Cumulative incidence of acute and chronic GVHD at 100 days and 1 year
2) Non-relapse mortality at 100 days and 1 year
3) Relapse/progiression at 100 days and 1 year
4) Overall survival and progression free survival at 100 days and 1 year
5) GVHD-free relapse free survival at 100 days and 1 year
6) Regimen related toxicity within 100 days after transplantation
7) Non-infections fever within 7 days after transplantation
8) Neutrophil and platelet engraftment and primary or secondary graft failure within 100 days and 1 year after transplantation
9) Infectious events within 100 days and 1 year after transplantation
10) The proportion of patients who stopped immunosuppressive drugs within 1 year after transplantation
11) Immune reconstitution using multi-color flowcytometer
12) Subgroup analysis according to stem cell source (BM or PB)
13) Subgroup analysis according to HLA disparity
14) Subgroup analysis according to stem cell count
15) Subgroup analysis according to primary disease and disease risk index

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: < 70age old
• Gender: Both

Include criteria

Patients meet all of the following criteria (1-6) :
1) Age >= 16 and <70 years old
2) ECOG Performance Status 0 or 1
3) Normal function of major organs
4) Major Indication
a) AML
Refractory to 1st induction therapy
Relapse after chemotherapy
Unfavorable chromosome abnormality including del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q,
17q, t(6;9), t(9;22) or complex karyotype
Normal karyotype and FLT3-ITD mutation
Intermediate/poor group by JALSG score
AML with MRC
History of relapse after allo-HSCT
CR1 with standard risk or high risk
(b) ALL
Refractory to 1st induction therapy, MRD positive or unevaluable
Relapse after chemotherapy
Any of the following poor prognostic factors
i) t(9;22) or t(4;11)
ii) >= 35 years of age at diagnosis
iii) WBC count of more than 30,000/uL for B-ALL, or more than 100,000/uL for T-ALL at diagnosis
History of relapse after allo-HSCT
History of relapse after CAR-T therapy
(c) Acute leukemias of ambiguous lineage
Refractory to the first induction therapy
Relapse after chemotherapy
Unfavorable chromosome abnormality
History of relapse after allo-HSCT
(d) MDS
EB-1 or 2
IPSS intermediate-2 or high
Transfusion dependent
History of relapse after allo-HSCT
(e) CML
AP or BC: refractory to multiple TKIs
CP beyond 1st CP or AP
History of relapse after allo-HSCT
(f) ATLL
Acute or lymphoma type in the SD or better
(g) ML
Malignant lymphoma which is classified in the WHO classification (revised 4th edition) which relapse
after auto-HCT or CAR-T therapy, or which have no indication for auto-HCT or CAR-T therapy due to
no sensitivity to chemotherapy or poorly controlled disease with conventional chemotherapy
(h) The disease which is approved as an indication of allo-HSCT in our conference
5) Patients who have a HLA 1-2 allele-mismatched unrelated donor and have no HLA matched relate
d or unrelated donor
6) Informed consent has been acquired

Exclude criteria

1) Major organ dysfunction
a) Total bilirubin: >= 2.0 mg/dl
b) Serum creatinine: >= 2.0 mg/dl
c) Left ventricular ejection fraction: < 50%
d) Pulmonary function test: %VC < 40%, FEV1.0% <50% or SpO2 <90% on room air
e) AST or ALT >= 3 x UNL
2) Uncontrolled active infection
3) Uncontrolled CNS invasion
4) Poorly controlled insulin-treated diabetes mellitus
5) Poorly controlled hypertension
6) Patients with a severe complication including heart failure, coronary failure, acute myocardial infarction within the last three months, liver cirrhosis and uncontrolled interstitial pneumonia
7) Pregnant, lactating woman or woman of childbearing potential
8) Patients with a severe mental disorder who are likely to be unable to participate in the study
9) HIV antibody positivity
10) A history of hypersensitivity or allergy to cyclophosphamide, tacrolimus or mycophenolate mofetil
11) Plan for administration of ATG for conditining or GVHD prophylaxis
12) The physician in charge determines that there is no indication to perform this intervention
(Note: HBs antigen positivity and HCV antibody positivity is not exclusion criterion. The positivity o
f donor-specific antigen (DSA) is not excluded but DSA with MFI >=5000 should be avoided as much
as possible.)

Related Information

• Primary Sponsor: Kuno Masatomo
• Secondary Sponsor: Nakamae Hirohisa