A Study Comparing C Pola R-CHP+X With CR-CHOP in the Treatment of Previously Untreated DEL Under the Guidance of Genotyping

Official title

A Prospective, Open-label, Multicenter, Randomized Controlled Study Comparing C Pola R-CHP+X With CR-CHOP in the Treatment of Previously Untreated Double-expression Diffuse Large B-cell Lymphoma Under the Guidance of Genotyping

Overview

Evaluate the efficacy and safety of C Pola R-CHP+X compared to CR-CHOP in the treatment of previously untreated patients with DEL

Detailed description

This is a prospective, open-label, multicenter, randomized controlled clinical study conducted among previously untreated CD20-positive DEL participants. Subjects who meet the inclusion/exclusion criteria will be randomly assigned in a 1:1 ratio to either the test group or the control group after signing the informed consent form:

The experimental group first received one course of CR-CHOP regimen, and then the subsequent treatment was determined based on whether the ctDNA LFC reached 3 after one cycle of CR-CHOP treatment.

Perform ctDNA detection at C1D14, and continue CR-CHOP treatment for patients with C1D14 ctDNA LFC ≥ 3 until 6 cycles.

For patients with C1D14 ctDNA LFC \< 3, stratification based on gene subtypes is conducted into C1, C2-3, and TP53mut types, which determines the medication for the remaining 5 cycles. For C1 type, PD1 inhibitors are added; for C2 and C3 types, BTK inhibitors are added; for TP53mut type, decitabine is added.

If assigned to the control group, they will continue to receive CR-CHOP for up to 6 cycles.

After each chemotherapy session, a routine evaluation is conducted. After completing three sessions, a comprehensive objective efficacy evaluation is performed. Patients with CR or PR in the efficacy evaluation continue with the original treatment regimen. For patients with SD or PD, second-line salvage therapy is recommended. After completing all treatments, the first summary evaluation is conducted. Patients with CR enter maintenance therapy with chidamide (maintenance for 2 years is recommended unless intolerable toxicity occurs or disease progresses) or undergo autologous hematopoietic stem cell transplantation. If CR is not achieved, the second-line regimen should be switched. After a follow-up of 2 years, the second summary evaluation is conducted. Before treatment, patients with large tumors may be recommended for radiation therapy in the corresponding area based on the doctor's judgment after completing six sessions of treatment (radiation dose is 30-40 Gy; however, it mainly depends on specific treatment principles). Additionally, the treating physician may decide whether to perform radiation therapy for extranodal lesions based on specific circumstances.

Interventions

• Drug C-Pola-R-CHP+X
  The experimental group first received one course of CR-CHOP regimen, and then the subsequent treatment was determined based on whether the ctDNA LFC reached 3 after one cycle of CR-CHOP treatment. Perform ctDNA detection at C1D14, and continue CR-CHOP treatment for patients with C1D14 ctDNA LFC ≥ 3 until 6 cycles. For patients with C1D14 ctDNA LFC \< 3, stratification is based on gene subtypes, namely C1, C2-3, and TP53mut, which determines the medication for the remaining 5 cycles. For C1 sub
• Drug CR-CHOP
  If assigned to the control group, they will continue to receive CR-CHOP for up to 6 cycles.

Primary outcome measures

• Complete remission (CR) rate [Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]

Secondary outcome measures (2)

• 2-year progression-free survival (PFS) rate [Time frame: 2 years after enrollment]
• 2-year overall survival (OS) rate [Time frame: 2 years after enrollment]

Eligibility criteria

Inclusion criteria

• 1\. Histopathological diagnosis confirmed as diffuse large B-cell lymphoma, with CD20 positivity;
• 2\. Simultaneous expression of MYC and BCL2, according to the WHO standard for immunohistochemistry: MYC ≥ 40%, BCL2 ≥ 50%
• 3\. Age ≥ 18 years old and ≤ 75 years old;
• 4\. ECOG performance status score of 0, 1, or 2;
• 5\. International Prognostic Index (IPI) > 1
• 6\. No history of malignant tumor; no concurrent occurrence of other tumors;
• 7\. Patients with an expected lifespan of at least 6 months, as determined by the researcher;
• 8\. The patient or their legal representative must provide written informed consent before undergoing any special examinations or procedures in the study.

Exclusion criteria

• 1\. Have previously received systemic or local treatments, including chemotherapy;
• 2\. Have previously undergone autologous stem cell transplantation;
• 3\. Previously had a history of other malignant tumors, excluding basal cell carcinoma and cervical carcinoma in situ;
• 4\. Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, severe infectious diseases, etc;
• 5\. Primary central nervous system lymphoma;
• 6\. Left ventricular ejection fraction (LVEF) is less than or equal to 50%;
• 7\. Laboratory test values during screening: (unless caused by lymphoma); A. Neutrophil count <1.5\*10\^9/L; B. Platelet count < 75 x 10\^9/L; C. ALT or AST is 2 times higher than the upper limit of normal, and AKP and bilirubin are 1.5 times higher than the upper limit of normal; D. Creatinine level is higher than 1.5 times the upper limit of normal;
• 8\. Other concurrent and uncontrolled medical conditions that the researcher believes will affect the patient's participation in the study.
• 9\. Patients with mental illness or other patients known or suspected to be unable to fully comply with the study protocol;
• 10\. Pregnant or lactating women;
• 11\. Individuals infected with HIV.
• 12\. Patients with positive HBsAg test results must undergo HBV DNA testing and can only be enrolled after becoming negative. Additionally, if the HBsAg test result is negative but the HBcAb test result is positive (regardless of the HBsAb status), HBV DNA testing is also required. If the result is positive, treatment must be administered until becoming negative before enrollment;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• No. 197 Ruijin 2nd Road, Huangpu District, Shanghai, Shanghai, Shanghai — Shanghai

Identifiers

NCT: NCT07511114 · C-pola-R-CHP+X

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗