Clinical trial NCT06649422: Reduced-Dose Chemo Followed by 14 Days of Blinatumomab for Newly Diagnosed Adult B-ALL Patients: a Multicenter Study
Official title: Clinical Study on the Efficacy and Safety of Reduced-Dose Chemotherapy Followed by 14 Days of Blinatumomab in Adult Patients with Newly Diagnosed Ph-Negative B-ALL: a Prospective, Multicenter, Observational Study.
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Leukemia, Lymphocytic, Acute, Adult
Keywords: blinatumomab
newly diagnosed Ph-chromosome negative acute B-lymphoblastic leukemia
induction treatment
reduced-dose chemotherapy
Lead sponsor: Shandong University
Sponsor class: OTHER
Collaborators: name: Shandong Provincial Hospital
name: The Affiliated Hospital of Qingdao University
name: Tangshan Central Hospital
name: Affiliated Central Hospital of Shandong First Medical University
name: Yantai Yuhuangding Hospital
name: Qilu Hospital of Shandong University (Qingdao)
name: Qingdao Central Hospital
name: Qingdao Municipal Hospital
name: The Affiliated Hospital of Jining Medical University and Zaozhuang City
name: Affiliated Hospital of Binzhou Medical College
name: Linyi People's Hospital
name: The Second Hospital of Shandong University
name: Affiliated Hospital of Shandong University of Traditional Chinese Medicine Hospital
name: Shandong First Medical University
name: Shengli Oilfield Hospital
name: Heze Municipal Hospital
name: Zibo Central Hospital
name: Zaozhuang Municipal Hospital
name: Weihai Municipal Hospital
First posted: 2024-10-18
Enrollment: 36
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 15-65 years newly diagnosed with Philadelphia chromosome-negative acute B-lymphoblastic leukemia, confirmed at Qilu Hospital of Shandong University and other participating institutions in Shandong Province.

Brief summary: This is a prospective, multicenter, observational study aimed at exploring the efficacy and safety of reduced-dose chemotherapy followed by frontline therapy with blinatumomab in patients aged 15-65 with newly diagnosed Ph-negative B-ALL.

Detailed description: The 14-day blinatumomab combined with reduced-dose chemotherapy is used for the induction treatment of newly diagnosed Ph-chromosome negative acute B-lymphoblastic leukemia. On day 14, an intrathecal injection of chemotherapy is administered; on days 28-35, bone marrow is assessed, and patients who do not achieve complete remission are withdrawn from the study. Patients with positive minimal residual disease (MRD) after induction treatment undergo transplant typing and proceed to allogeneic hematopoietic stem cell transplantation (Allo-HSCT) after early intensification. Patients with negative MRD receive alternating treatment with multi-drug combination chemotherapy and blinatumomab, for a total of 8 consolidation courses, including 3 courses of blinatumomab. Maintenance therapy lasts for at least 18 months, using the POMP regimen with or without one cycle of blinatumomab every six months. Throughout the entire treatment phase, at least 12 preventive intrathecal injections are administered.

Eligibility criteria: Inclusion Criteria:

* Age 15-65 years, both male and female are eligible;
* Untreated newly diagnosed Ph-negative B-ALL patients; Diagnosis is defined by using morphological, immunological, cytogenetic, and molecular (MICM) diagnostic models, with immunotyping showing \>20% primitive lymphoid cells in the bone marrow; bone marrow cytogenetics showing Philadelphia chromosome (Ph) negative (after observing at least 20 metaphases) and/or fluorescence in situ hybridization (FISH) BCR/ABL negative and/or molecular BCR/ABL fusion gene negative;
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2;
* Organ function tests must meet all the following criteria: Total bilirubin \<1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \<2.5×ULN (if liver is involved, then ALT and AST \<5×ULN are allowed); Creatinine \<1.5×ULN; Serum amylase and lipase ≤1.5×ULN; Alkaline phosphatase ≤2.5× ULN; Serum electrolytes potassium, magnesium, phosphorus within normal limits.
* Cardiac color Doppler echocardiography ejection fraction ≥45%;
* Female patients of childbearing potential must have a negative pregnancy test (within 7 days prior to enrollment).

Exclusion Criteria:

* Previous or ongoing systemic anti-acute lymphoblastic leukemia (ALL) treatment (including but not limited to radiotherapy), except for appropriate pretreatment;
* Clinical manifestations of central nervous system or extramedullary involvement at the time of diagnosis;
* Patients participating in other clinical studies simultaneously;
* Accompanying diseases that, in the judgment of the investigator, pose a serious risk to patient safety or affect the patient's ability to complete the study;
* A history of definite neurological or psychiatric disorders, including epilepsy or dementia;
* Major surgery within the last 4 weeks or not recovered from previous surgery;
* Having other malignant tumors, unless the other primary malignant tumor is currently stable or does not require active intervention;
* Women of childbearing age or men who cannot use sufficient methods for contraception, including pregnant or lactating women;
* Clinically significant severe uncontrollable heart disease (including but not limited to a history of myocardial infarction, stroke, or revascularization; unstable angina or transient ischemic attack within 6 months before enrollment; congestive heart failure or left ventricular ejection fraction (LVEF) below the local institutional standard lower limit within 6 months before enrollment; a history of clinically significant (determined by the attending physician) atrial arrhythmia; a history of ventricular arrhythmia; a history of venous thromboembolism, including deep vein thrombosis or pulmonary embolism, uncontrollable hypertension, etc.);
* Confirmed positive status for human immunodeficiency;
* Active severe infections that cannot be controlled by oral or intravenous antibiotics;
* Patients known to be allergic or contraindicated to the study drug (active pharmaceutical ingredient and/or excipients);
* Existence of bleeding disorders unrelated to ALL.

Primary outcomes:
measure: The overall response rate
timeFrame: At the end of induction treatment from day 28 to day 35
measure: Minimal Residual Disease (MRD) negativity rate after induction therapy
timeFrame: At the end of induction treatment from day 28 to day 35
Secondary outcomes:
measure: Complete molecular remission rate.
timeFrame: At the end of induction treatment from day 28 to day 35
measure: One-year overall survival rate.
timeFrame: From diagnosis of the disease to the end of the first year
measure: One-year event-free survival rate
timeFrame: From diagnosis of the disease to the end of the first year
measure: Safety
timeFrame: From enrollment until withdrawal from the study or the end of follow-up up to two years
Other outcomes:
Locations:
Study officials:
affiliation: Qilu Hospital of Shandong University
name: Chunyan Ji, Doctor
role: PRINCIPAL_INVESTIGATOR
References: