HLA-mismatched HSCT for high-risk hematological disease with adjusted immunosuppressabts and low-dose alemtuzumab

JRCT ID: jRCTs031180237

Registered date:12/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Patients with high-risk advanced hematological disease
• Date of first enrollment: 11/08/2015
• Target sample size: 43
• Study type: Interventional

Intervention(s)

Conditioning regimen: Patients who are intolerable to conventional conditioning regimen due to either higher age (55>=), previous ASCT, organ dysfunction, or active infection will receive regimen 2-1 or 2-2. (Mainly, regimen 2-1 will be selected in patients with lymphoid malignancy and regimen 2-2 will be selected in patients with myeloid malignancy.) In patients who were not eligible for TBI-containing regimen, regimen 2-3 may be selected. The other patients will receive regimen 1.

Regimen 1
Cyclophosphamide
60mg/kg/day iv. for 2 days
TBI
2Gy twice daily for 3 days
Alemtuzumab
0.25mg/kg/day iv. day-4,-3
(Maximum dose: 15mg/body/day for 2 days)
*Cytarabine 2g/m2 twice/day iv. for 2-3 days
or etoposide 15ng/kg/day iv. for 2 days may be added.
*Cyclophosphamide may be replaced with fludarabine 30mg/m2/day iv. for 4 days

Regime 2-1
Fludarabine
25mg/m2/day iv. for 5 days
Melphalan
40mg/m2/day iv. for 2 days
Alemtuzumab
0.25mg/kg/day iv. day-4,-3
(Maximum dose: 15mg/body/day for 2 days)

Regimen 2-2
Fludarabine
30mg/m2/day iv. for 6 days
Busulfan
3.2mg/kg/day iv. for 2-4 days
TBI
2Gy once or twice daily for 1 day
Alemtuzumab
0.25mg/kg/day iv. day-4,-3
(Maximum dose: 15mg/body/day for 2 days)

Regimen 2-3
Fludarabine
30mg/m2/day iv. for 6 days
Busulfan
3.2mg/kg/day iv. for 4 days
Melphalan
80-140mg/m2/day iv. for 1 days
Alemtuzumab
0.25mg/kg/day iv. day-4,-3
(Maximum dose: 15mg/body/day for 2 days)

Outcome(s)

• Primary Outcome: Survival rate at 60 days after transplantation with the engraftment of donor cells and without grade III-IV GVHD
• Secondary Outcome: Relapse rate, non-relapse mortality, and overall survival at 1 year

Key inclusion & exclusion criteria

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

Include criteria

1.Patients who do not have an available HLA-matched or one locus-mismatched related donor.
2.Patients who have a two- or three-locus-mismatched haploidentical related donor in good condition. (This donor should precede an HLA-matched or one locus-mismatched related donor according to the disease status.)
3.Patients who do not have an HLA-matched or one allele-mismatched unrelated donor, or patients whose disease status preclude time-consuming donor coordination.
4.Patients with high-risk advanced hematological disease. Leukemia and malignant lymphoma in non-remission, MDS with more than 20% of blast, and relapsed disease after allogeneic transplantation are included in high-risk group.
5.Patients who are 16 to 70 years old
6.Patients in performance status of 0 or 1.
7.Patients whose major organ functions are preserved.

Exclude criteria

1.Patients with poorly controlled active infection.
2.Patients with coexistence of malignancy.
3.Patients who are pregnant or nursing.
4.Patients with serious mental disorder.
5.Patients with HIV antibody positive.
6.Patients who are allergic to drugs used in conditioning regimen or GVHD prophylaxis.

Related Information

• Primary Sponsor: Kanda Yoshinobu
• Secondary ID(s): UMIN000018298