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Active, not recruiting Phase 1

Phase Ib Study of Rocbrutinib in Combination With R-CHOP in Patients With Newly Diagnosed B-cell Non-Hodgkin Lymphoma

NCT06251180 · tracked via the Priya Life Science China tracker
Phase
Phase 1
Started
2024-04-10
Last updated
2026-09-11

Condition(s) studied

B-cell Non-Hodgkin Lymphoma

Investigational drug(s) / intervention(s)

Rocbrutinib →Rituximab →Cyclophosphamide →doxorubicin →Vincristin →Prednisone →

Rocbrutinib: orally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.

Rituximab: 375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.

Cyclophosphamide: 750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.

doxorubicin: 50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.

Vincristin: 1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.

Prednisone: 100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.

Study summary

This is an open-label, multicentre Phase Ib study to evaluate the safety and preliminary efficacy of new generation Bruton Tyrosine Kinase inhibitor Rocbrutinib in combination to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, Prednison) in adult patients with newly diagnosed, previously untreated B-cell Non-Hodgkin Lymphoma \[Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL) or Mantle Cell Lymphoma (MCL)\].

Eligibility

Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria: * Participants was histopathologically diagnosed with any of the following diseases: DLBCL, MZL or MCL (if enrolled in the dose expansion phase, histological confirmation of non-GCB subtype), and have not previously received anti-tumor systemic therapy or local radiation therapy for the above diseases. * Participants must have at least one measurable lesion. * ECOG physical status score 0-2. * Life expectancy ≥6 months. * International Prognostic Index (IPI) score ≥ 2 (only participants with DLBCL in dose expansion portion). * Adequate coagulation, liver, kidney, and hematopoietic functions:PT and APTT \<1.5x ULN; serum bilirubin \<1.5x ULN except in participants with Gilbert's syndrome who must have a serum bilirubin of \<3x ULN, AST and ALT ≤ 3x ULN or \< 5x ULN if hepatic involvement are present; serum creatinine (Scr) ≤1.5 x ULN, or calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula.; ANC≥1500/mm3, hemoglobin≥8.0 g/dL, and platelets \>100,000/mm3 unless deemed related to lymphoma involvement in the bone marrow and felt potentially reversible by the treating physician. * Women of childbearing potential must have a negative serum or urine (beta-human chorionic gonadotropin \[beta-hCG\]) at screening. * Women of childbearing potential and men who are sexually active with a woman of childbearing potential must be practicing a highly effective contraceptive measures of during and after the study (90 days after the last dose of ROCBRUTINIB and 12 months after the last dose of Rituximab). Men must agree to not donate sperm during and for up to 90 days after he last dose of ROCBRUTINIB. * Participants voluntarily enrolled and signed the informed consent form, and followed the trial treatment and visits. Exclusion Criteria: * Participants are allergic to Rocbrutinib or any of its excipients; Participants who are assessed by the investigator as being unable to tolerate the R-CHOP regimen. * Participants with known central nervous system involvement with lymphoma. or diagnosis of primary central nervous system lymphoma (PCNSL) or primary mediastinal large B-cell lymphoma (PMBL). * Participants with DLBCL had a history of indolent lymphoma such as FL or CLL (Richter's transformation), or was histopathologically comfirmed with FL (regardless of grade) coexistentially. * Prior treatment with solid organ transplantation or hematopoietic stem cell transplantation(HSCT) ; expected HSCT during the study. * Major surgery within 4 weeks of study entry or expected major surgery during the study. * Prior another non-antitumor or medical instruments clinical trials within 4 weeks. * Known bleeding diseases (such as von Willebrand's disease or hemophilia A, hemophilia B, etc.), or have bleeding tendency. * Prior treatment with warfarin or equivalent vitamin K antagonists within 14 days; requires anticoagulation with warfarin or equivalent vitamin K antagonists. * Prior treatment with strong/moderate CYP3A4 inhibitors within 5 days or prior foods with inhibitory effects on CYP3A4 within 3 days at screening; requires chronic treatment with moderate/strong CYP3A inhibitors or inducers, or OATP1B1/OATP1B3 sensitive substrates during the study. * Participants with other malignancies other than the target indications of this study within the past three years. * Prior treatment with the cumulative dose of doxorubicin ≥150 mg/m2 (or other anthracyclines at doses converted based on cumulative cardiac toxicity) * Any serious medical condition including but not limited to uncontrolled hypertension, uncontrolled congestive heart failure or ≥Class 2 cardiac disease as defined by the New York Heart Association Functional Classification or LVEF less than 40%, uncontrolled or symptomatic arrhythmias with corrected QT interval (QTc) \> 480 msec, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, COPD, renal failure, severe hepatic disease, uncontrolled active infection, active hemorrhage. * Known HIV infection, or syphilis infection, or hepatitis B DNA or hepatitis C RNA positive. * Known diseases that affect drug swallowing or absorption. * Unfit to participate in this study in the investigator's opinion.

Primary outcome measure(s)

  • MTD — Up to 21 days after the initial dose
    Standard phase I 3+3 design.
  • Recommended Dose — Up to 1.5 years
    Recommended Dose will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
  • Incidence of AEs — From first dose of study drug to 28 days after the last dose of study drugs
    Type, frequency and severity of AEs, relationship of AEs to study treatment Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Type, frequency and severity of AEs, relationship of AEs to study treatment Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
  • Incidence of clinically significant laboratory abnormalities — From first dose of study drug to 28 days after last dose of study drug
    Clinically significant abnormalities in hematology, chemistry, coagulation and urinalysis.
  • Cmax of Rocbrutinib — Up to 24 hours post dose
    Maximum plasma concentration (Cmax) of Rocbrutinib.
  • Tmax of Rocbrutinib — Up to 24 hours post dose
    Time to maximum plasma concentration (Tmax) of Rocbrutinib.
  • T1/2 of Rocbrutinib — Up to 24 hours post dose
    The terminal elimination half-life (t1/2).
  • AUC0-t of Rocbrutinib — Up to 24 hours post dose
    Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration of Rocbrutinib.
  • CL/F of Rocbrutinib — Up to 24 hours post dose
    Apparent clearance (CL/F) of Rocbrutinib.

Trial sites (1)

FacilityCityRegionStatus
Sun Yat-sen University Cancer Center Guangzhou Guangdong
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06251180 on ClinicalTrials.gov ↗ ← All trials in China