HLA-haploidentical HSCT with reduced dose of PTCy

JRCT ID: jRCTs051180144

Registered date:20/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Hematological malignancy
• Date of first enrollment: 09/02/2017
• Target sample size: 33
• Study type: Interventional
• Intervention(s): Fludarabine (15 mg/square meter of body surface area twice a day for 2 days and 30 mg/square meter once a day for 4 days), cytarabine (2 g/square meter twice a day for 2 days), and melphalan (100 mg/ square meter per day for 1 day) are used as a conditioning regimen. Cyclophosphamide 50 mg/kg is given on day 3, 25 mg/kg on day 4 after the graft infusion. The donor source is peripheral blood stem cell. Continuous intravenous tacrolimus (0.03 mg/kg/day) and oral mycophenolate mofetil 1,000 mg three times a day are initiated from day 5 after transplantation.

Outcome(s)

• Primary Outcome: Proportion of patients who survive with graft engraftment at 100 days fo1lowing transplantation

Secondary Outcome

1) Overall survival, relapse rate
2) Non-relapse mortality
3) Incidence and severity of acute and chronic GVHD
4) Incidence of primary and secondary engraftment failure
5) Time to hematopoietic recovery, time to complete donor chimerism
6) Regimen related toxicity
7) Incidence of bacterial, fungal and viral infections
8) Immune reconstruction
9) Relation between donor peripheral blood stem cells and prognosis

Key inclusion & exclusion criteria

• Age minimum: >= 15age old
• Age maximum: < 70age old
• Gender: Both

Include criteria

Among patients with refractory hematological disorders (indicated in the selection criteria) who are clinically adopted to allo-HSCT because they cannot expect to be cured or long-term survival by any other therapy, patients who do not have or not available HLA serological identical related donors and have HLA-haploidentical donors.

1) Age >= 15 and < 70 years old
2) ECOG PS 0 or 1
3) Normal function of major organs
4) Informed consent has been acquired

5)Indication
(a) AML
1. Refractory to 1st induction therapy
2. Relapse after chemotherapy
3. 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
4. Normal karyotype and FLT3-ITD mutation
5. Intermediate/poor group by JALSG score
6. AML with MRC
7. History of relapse after allo-HSCT
8. CR1 with standard risk or high risk
(b) ALL
1. Refractory to 1st induction therapy
2. Relapse after chemotherapy
3. 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
4. History of relapse after allo-HSCT
(c) Acute leukemias of ambiguous lineage
1. Refractory to the first induction therapy
2. Relapse after chemotherapy
3. Unfavorable chromosome abnormality
4. History of relapse after allo-HSCT
(d) MDS
1. RAEB-1 or 2
2. IPSS intermediate-2 or high
3. Transfusion dependent
4. History of relapse after allo-HSCT
(e) CML
1. AP or BC: refractory to multiple TKIs
2. CP beyond 1st CP or AP
3. History of relapse after allo-HSCT
(f) ATLL, ML
1. ATLL
Acute or lymphoma type in the PR or better
2. ML
Malignant lymphoma which is classified in the 2008 WHO classification which relapse after auto-HSCT, or which have no indication for auto-HSCT due to no sensitivity to chemotherapy or poorly controlled disease with conventional chemotherapy

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 SaO2 <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 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) A history of hypersensitivity or allergy to any drugs in the conditioning regimen of this transplant
10) HIV antibody positivity
11) A history of administration of mogamulizumab
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)

Related Information

• Primary Sponsor: Nakamae Hirohisa
• Secondary Sponsor: Hino Masayuki
• Secondary ID(s): UMIN000026028