Reduced-Dose Chemo Followed by 14 Days of Blinatumomab for Newly Diagnosed Adult B-ALL Patients: a Multicenter Study

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Leukemia, Lymphocytic, Acute, Adult
• Intervention / Treatment: Drug: Blinatumomab

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is administered; on days 28-35, bone marrow is assessed, and patients who do not achieve complete remission are withdrawn from the study.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.

• Study Type: Observational
• Enrollment (Estimated): 36

Contacts and Locations

• Study Contact: Name: Yanping Sun; Phone Number: 18560089133; Email: syp215920@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Reduced-dose chemotherapy followed by blinatumomab induction treatment group; Patients aged 15-65 with newly diagnosed Ph-negative B-ALL undergoing frontline induction therapy with reduced-dose chemotherapy followed by blinatumomab.	Drug: Blinatumomab; 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.; Other Names: Combination chemotherapy with multiple drugs.; preventive intrathecal injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall response rate	The overall response rate after induction therapy = Complete Remission (CR) + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (Cri).	At the end of induction treatment from day 28 to day 35
Minimal Residual Disease (MRD) negativity rate after induction therapy	MRD negativity refers to a flow cytometry test result where MRD is less than 0.01%.	At the end of induction treatment from day 28 to day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete molecular remission rate.	Complete molecular remission rate is defined as undetectable Ig rearrangement by next-generation sequencing, with a detection sensitivity of at least less than 10^-5.	At the end of induction treatment from day 28 to day 35
One-year overall survival rate.	The proportion of patients who are still alive one year after the date of disease diagnosis, out of the total number of subjects enrolled in the study.	From diagnosis of the disease to the end of the first year
One-year event-free survival rate	The proportion of patients who have not experienced disease progression, been diagnosed with another cancer, or died from any cause one year after the date of disease diagnosis, out of the total number of subjects enrolled in the study.	From diagnosis of the disease to the end of the first year
Safety	Safety endpoints are defined, graded, and evaluated according to the CTCAE version 5.0 criteria.	From enrollment until withdrawal from the study or the end of follow-up up to two years

Collaborators and Investigators

• Sponsor: Shandong University
• Collaborators: The Affiliated Hospital of Qingdao University; Shandong Provincial Hospital; Qingdao Municipal Hospital; The Second Hospital of Shandong University; Qingdao Central Hospital; Yantai Yuhuangding Hospital; Zibo Central Hospital; Weihai Municipal Hospital; Qilu Hospital of Shandong University (Qingdao); Zaozhuang Municipal Hospital; Heze Municipal Hospital; Shengli Oilfield Central Hospital; Linyi Central Hospital; The Affiliated Hospital of Jining Medical University and Zaozhuang City; Tangshan Central Hospital; Affiliated Hospital of Shandong University of Traditional Chinese Medicine Hospital; The First Affiliated Hospital of Shandong First Medical University; Affiliated Central Hospital of Shandong First Medical University; Affiliated Hospital of Binzhou Medical College
• Investigators: Principal Investigator: Chunyan Ji, Doctor, Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: blinatumomab; induction treatment; newly diagnosed Ph-chromosome negative acute B-lymphoblastic leukemia; reduced-dose chemotherapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: QLCR20240289

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No