Clinical trial NCT06250959: RDC-Blinatumomab Versus hyperCVAD for Ph-negative B-ALL.
Official title: Comparing the Efficacy and Safety of Reduced-dose Chemotherapy Followed by Blinatumomab Versus hyperCVAD as Induction Therapy for Newly Diagnosed Ph-negative B-ALL: a Multicenter, Radomized, Phase 2 Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: ALL, Adult
Philadelphia-Negative ALL
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-02-09
Enrollment: 124
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and 1:1 randomised into Reduced-intensity chemotherapy followed by Blinatumomab cohort or hyperCVAD cohort as induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated.

Detailed description: Blinatumomab, a CD3/CD19 bisespecific T-cell conjugative antibody, has shown high efficacy in phase I/II studies of relapsed/refractory B-lymphoblastic leukemia (B-ALL), particularly in the context of low tumor burden.Meanwhile, Blinatumomab also plays an important role in rapid and efficient clearance of MRD in patients. Therefore, its use in combination with less intensive chemotherapy for initial induction therapy in newly diagnosed patients may result in favorable response rates, greater depth of remission, and lower treatment-related toxic effects.

In this study, newly diagnosed non-elderly patients with Philadelphia chromosomal negative (PH-) B-ALL were enrolled and 1:1 randomised into Reduced-intensity chemotherapy followed by Blinatumomab cohort or hyperCVAD cohort as induction therapy. The clinical remission rate, MRD negative rate and treaty-related adverse reactions were evaluated.

The regimen of consolidation therapy is recommended as multidrug combination chemotherapy (including high-dose Methotrexate or Cytarabine combined with Asparaginase) or alternating with Blinatumomab (28 ug/d×28d). If Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is not performed, consolidation therapy needs at least 4 courses before 2 years maintenance therapy.

Eligibility criteria: Inclusion Criteria:

* Age 15-65
* Ph-(BCR-ABL1 negative)B-ALL was diagnosed according to WHO diagnostic criteria
* Newly diagnosed patients without prior induction therapy (except hydroxyurea and glucocorticoids ≦5 days
* ECOG score 0-3
* Liver function: total bilirubin ≦ 3 times the upper limit of normal; Alanine ·aminotransferase ≦ 3 times upper limit of normal motion; Aspartate aminotransferase ≦ 3 times upper limit of normal motion; (except considering leukemia infiltration)
* Renal function: endogenous creatinine clearance ≧30ml/min
* Patients must be able to understand and willing to participate in the study and must sign the informed consent form.

Exclusion Criteria:

* Ph+ (BCR-ABL1 positive) ALL
* T cells ALL
* Mature B-cell leukemia/lymphoma, B-cell lymphoma, with extramedullary disease
* Acute mixed-cell leukemia
* Central nervous system leukemia
* HIV infection
* HBV-DNA or HCV-RNA positive
* Patients with grade 2 or higher heart failure and other patients deemed inappropriate for inclusion by the investigator
* Pregnant or breastfeeding patients
* The study patient was refused enrollment

Primary outcomes:
measure: Composite complete remission rate
timeFrame: Induction therapy phase: The time of bone marrow evaluation is day 28±7.
Secondary outcomes:
measure: The negative rate of minimal residual lesion (MRD)
timeFrame: Induction therapy phase: The time of bone marrow evaluation is day 28 ±7.
measure: Treatment-related AE
timeFrame: Induction therapy phase
measure: Quality of survival of patients in the induction therapy phase
timeFrame: Induction therapy phase
measure: Progression-free survival（PFS）
timeFrame: 1 year after study completion
measure: Overall survival (OS)
timeFrame: 1 year after study completion
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: Soochow U
name: Jing Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: