A multicenter trial to assess the safty and efficacy of post-transplanation maintenance therapy by blinatumomab for relapsed/refractory CD19 positive B-cell acute lymphoblastic leukemia

JRCT ID: jRCTs041210154

Registered date:03/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: B-cell precursor acute lymphoblastic leukemia
• Date of first enrollment: 25/04/2022
• Target sample size: 41
• Study type: Interventional
• Intervention(s): The patients who underwent allogeneic hematopoietic stem cell transplantation for B-cell acute lymphoblastic leukemia in non-remission or third complete remission (phase 1), or in disease stage beyond first complete remission (phase 2), and have to be 30-100 days from transplant with hematorogical recovery and without relapse and active acute graft-versus-host disease, will be eligible and be scheduled to receive 2 courses of Blinatumomab as a continuous intravenous infusion over 4 weeks with 2 weeks interval.

Outcome(s)

Primary Outcome

Phase I
Study treatment completion rate

Phase II
GvHD-free, relapse-free survival rate at 1 year after transplantation

Secondary Outcome

Phase I
Percentage of NCI-CTCAE ver5.0 grade 3 or higher adverse events within each course

Phase II
Incidence of GvHD at 1 year after transplantation
Incidence of secondary graft failure at 1 year after transplantation
Incidence of relapse at 1 year after transplantation
Non-relapse mortality rate at 1 year after transplantation
Disease-free survival rate at 1 year after transplantation
Overall survival rate at 1 year after transplantation
Percentage of NCI-CTCAE ver5.0 grade 3 or higher adverse events within each course

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 25age old
• Gender: Both

Include criteria

1) Patients with CD19 positive precursor B-Cell Acute Lymphoblastic Leukemia, younger than 25 years old at the time of enrollment
2) ECOG-PS 2 or less
3) Clinica stage at the time of receiving allogeneic hematopoietic stem cell transplantation;
Clinical stage beyond the first complete remission.
4) At the time of enrollment, patients must have achieved a neutrophil count of 0.5x10^9/L or higher without 48 hours of G-CSF administration and a platelet count of 20,000 or higher without 72 hours of platelet transfusion at least 30 days but less than 100 days after transplantation.
5) Hematological remission is confirmed by bone marrow test performed at the time of enrollment
6) Written informed consent obtained from patient or guardians.

Exclude criteria

1) If antileukemic agents other than blinatumomab is administered after transplantation for the purpose of treating the primary disease
2) Active grade 2-4 acute GvHD or moderate to severe chronic GvHD at the time of enrollment, and immunosuppressive drugs (including systemic steroids) are being administered for the treatment of GvHD. Administration of immunosuppressive agents for the prevention of GvHD is acceptable. Topical steroids for acute grade 1 GvHD (skin manifestations up to stage 2) are acceptable.
3) If central nervous system lesions are present at the time of enrollment
4) Less than 20% of CD19 expression rate of blasts assessed at the diagnosis or relapse
5) Four or more consecutive courses of blinatumomab up to just before the start of the pre-transplant conditining regimen
6) Have enrolled in this study after a previous transplantation
7) Have an active infection at the time of enrollment
8) At the time of enrollment, patients have any of the following: hepatic impairment (AST/ALT >5xULN, T-Bil >2.5xULN), renal impairment (Cre >2xULN), respiratory impairment requiring oxygenation, heart failure with EF <40%, or neurological disease with frequent seizures
9) HIV antibody positive, HBs antigen positive or HCV antibody positive
10) Women who are pregnant or may become pregnant
11) If the principal investigator or sub-investigator judges that participation in this study is not appropriate.

Related Information

• Primary Sponsor: Sakaguchi Hirotoshi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development