the Efficacy of Leucogen in Preventing the Risk of Ribociclib-Associated Neutropenia in Early Breast Cancer

NCT07380646 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-1460
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multicenter, single-arm, open-label Phase II exploratory clinical trial designed to evaluate whether prophylactic use of leucogen can reduce the incidence of Grade 3 or higher neutropenia in early-stage HR+/HER2- breast cancer patients receiving ribociclib combined with endocrine therapy. The study plans to enroll 97 patients using a Simon two-stage design, with the primary endpoint being the incidence of severe neutropenia within 4 treatment cycles (4 months) after initiation. Secondary endpoints include the incidence of all-grade neutropenia, febrile neutropenia, ribociclib treatment intensity, and safety. The study will systematically assess the preventive efficacy and safety of leucogen to provide a basis for subsequent Phase III randomized controlled trials.

Conditions

Neutropenia (Low White Blood Cell Count); Breast Cancer; Leucogen; Ribociclib

Outcome Measures

Primary Outcomes (1)

• incidence of severe neutropenia

  Complete blood count (CBC) should be performed on Day 1 and Day 21 of each treatment cycle. A decrease in the absolute neutrophil count (ANC) to \< 1000-500/mm³ (which is equivalent to \< 1.0-0.5 × 10⁹/L) is defined as severe neutropenia.

  From enrollment to the end of treatment at 16 weeks

Study Arms (1)

Leucogen combined with Ribociclib (Kisqali®) and Endocrine Therapy (e.g., Letrozole, Anastrozol)

EXPERIMENTAL

The experimental arm receives ribociclib at the standard dose (orally, 400mg, once daily on days 1-21 of a 28-day cycle) combined with a specified endocrine therapy (e.g., letrozole or anastrozole) plus leucogen (40mg orally three times daily on days 8-28 of a 28-day cycle).

Drug: Treat Regimen

Interventions

Treat Regimen DRUG

leucogen combined with ribociclib and endocrine therapy

Leucogen combined with Ribociclib (Kisqali®) and Endocrine Therapy (e.g., Letrozole, Anastrozol)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has signed and dated the informed consent form.
• Age \> 18 years at the time of signing informed consent.
• The patient is a female with known menopausal status at the time of signing informed consent or initiation of adjuvant endocrine therapy (whichever is earlier). Postmenopausal status is defined as: bilateral oophorectomy, age \> 60 years, or age \< 60 years with amenorrhea ≥ 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression), and follicle-stimulating hormone and plasma estradiol levels within the local postmenopausal normal range.
• Histologically confirmed unilateral primary invasive breast cancer, with the date of initial cytological or histological diagnosis within 18 months before enrollment. Patients with multicentric and/or multifocal tumors are eligible if all pathologically examined lesions meet criteria 5 and 6 below.
• Estrogen receptor (ER) and/or progesterone receptor (PgR) positivity in the breast cancer, based on the most recent analyzed tissue sample from the local laboratory.
• HER2-negative breast cancer, defined as negative by in situ hybridization or immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization result is required to confirm HER2-negative status (based on the most recent analyzed tissue sample from the local laboratory).
• The patient has undergone surgical resection with complete tumor removal, negative microscopic margins on the final surgical specimen, and belongs to one of the following categories:
• Anatomic Stage II, with any of the following: T0-2N1, T3N0, T2N0 with Grade 2 and Ki-67 ≥ 20%, T2N0 with Grade 2 and high-risk genomic assay result, T2N0 with Grade 3.
• Anatomic Stage III. High-risk genomic assay is defined as Oncotype DX Recurrence Score ≥ 26, or high-risk group by Prosigna PAM50, MammaPrint, or EndoPredict.
• If clinically indicated, the patient has completed adjuvant and/or neoadjuvant chemotherapy according to guidelines before screening.
• If clinically indicated, the patient has completed adjuvant radiotherapy according to guidelines before screening.
• The patient has no contraindications to the adjuvant endocrine therapy in the trial and plans to receive endocrine therapy for 5 years or longer starting from the randomization date.
• The patient may have received any standard neoadjuvant endocrine therapy at the time of signing informed consent, but enrollment must occur within 12 months of the first endocrine therapy initiation. Note: Endocrine therapy for ovarian suppression or short-term fertility preservation is not considered neoadjuvant/adjuvant endocrine therapy. If the patient is using tamoxifen as adjuvant endocrine therapy, a washout period of 5 half-lives is required before enrollment, during which the patient may take an aromatase inhibitor.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate bone marrow and organ function defined by meeting the following local laboratory values:

You may not qualify if:

• Previous treatment with any CDK4/6 inhibitor.
• Use of tamoxifen, raloxifene, or aromatase inhibitors for breast cancer risk reduction ("chemoprevention") and/or osteoporosis treatment within 2 years before signing informed consent.
• Prior anthracycline cumulative dose reaching or exceeding: doxorubicin 450 mg/m², or epirubicin 900 mg/m².
• Known hypersensitivity to any excipient of ribociclib and/or the endocrine therapy and/or leucogen (e.g., rare hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption, or soy allergy).
• Evidence of distant metastasis of breast cancer beyond regional lymph nodes (AJCC 8th edition Stage IV) and/or recurrence after curative surgery.
• Concurrent use of other anticancer therapies, except adjuvant endocrine therapy.
• Major surgery, chemotherapy, or radiotherapy within 14 days before enrollment.
• Clinical and laboratory acute toxicities related to prior anticancer therapy have not recovered to Grade 1 or lower (per NCI CTCAE version 4.03) on the day of enrollment. Exceptions: alopecia and amenorrhea of any grade are allowed.
• Current invasive malignancy, or previous invasive malignancy completed treatment within 2 years before signing informed consent. Note: Patients with past or concurrent in situ malignancy are eligible if they have undergone adequate curative treatment before enrollment.
• Known history of human immunodeficiency virus (HIV) infection.
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Clinically significant, uncontrolled cardiac disease and/or cardiac repolarization abnormalities, including any of the following:
• Documented history of myocardial infarction, angina, symptomatic pericarditis, or coronary artery bypass grafting within 6 months before trial enrollment.
• Documented cardiomyopathy. Left ventricular ejection fraction \< 50% as measured by multigated acquisition scan or echocardiography.
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or presence of any of the following risk factors: risk factors for torsades de pointes including uncorrected hypokalemia or hypomagnesemia, history of heart failure, or history of clinically significant/symptomatic bradycardia. Concurrent use of medications known to prolong the QT interval and/or known to cause TdP that cannot be discontinued or switched to a safe alternative (e.g., within 5 half-lives or 7 days before starting trial treatment). Inability to determine QTcF interval.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Breast surgery department

Hangzhou, Zhejiang, 310058, China

RECRUITING

MeSH Terms

Conditions

Neutropenia; Leukopenia; Breast Neoplasms

Condition Hierarchy (Ancestors)

Agranulocytosis; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Jing xin Jiang, Doctor

CONTACT

0571-89713716; 11418327@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-Arm, Phase II, Multicenter

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: February 2, 2026
• Study Start: January 7, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)