Orelabrutinib Combined With Obinutuzumab and Short-Course Venetoclax in Patients With Treatment-Naïve Mantle Cell Lymphoma (MCL)

Summary

This study aims to evaluate the safety and efficacy of orelabrutinib (O) in combination with obinutuzumab (G) and short-course venetoclax (V) in patients with treatment-naïve MCL.

Eligibility

Inclusion Criteria:

1. Voluntarily participate and sign the informed consent form;
2. Age ≥ 18 years, male or female;
3. Life expectancy ≥ 3 months;
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Patients with ECOG 3 may be enrolled only if the decline in performance status is attributed to the underlying disease and the investigator determines that they may benefit from the treatment;
5. Pathologically confirmed diagnosis of mantle cell lymphoma (MCL) and treatment-naïve;
6. Presence of measurable and/or evaluable lymphoma lesions;
7. Adequate bone marrow reserve, defined as: absolute neutrophil count \> 1.0×10⁹/L or platelet count \> 75×10⁹/L, unless cytopenias are considered to be related to bone marrow involvement by lymphoma and deemed recoverable by the investigator;
8. Hepatic function: AST (SGOT) and ALT (SGPT) ≤ 2.5 × upper limit of normal (ULN) (in the absence of liver involvement) or ≤ 5 × ULN (in the presence of liver involvement); total bilirubin (TBIL) ≤ ULN; serum creatinine (CRE) ≤ 1.5 × ULN;
9. Creatinine clearance ≥ 30 mL/min, calculated using the Cockcroft-Gault formula;
10. Able to comply with the study visit schedule and other protocol requirements;
11. All patients of childbearing potential must agree to use effective contraceptive measures during the study and for 24 months after study treatment discontinuation. Female patients of childbearing potential must have a negative urine pregnancy test prior to the first dose of study treatment.

Exclusion Criteria:

1. Received prior treatment for lymphoma within 2 weeks before study enrollment;
2. Any serious medical condition, including but not limited to:

   * Uncontrolled hypertension (defined as blood pressure that remains uncontrolled after at least 4 weeks of treatment with a reasonable and tolerable regimen of 3 or more antihypertensive agents \[including diuretics\] at adequate doses, or requiring 4 or more antihypertensive agents to achieve adequate control);

     * Uncontrolled congestive heart failure within 6 months prior to screening (New York Heart Association \[NYHA\] Class III \[moderate\] or Class IV \[severe\] cardiac disease);

       * Left ventricular ejection fraction (LVEF) \< 50%;

         * Symptomatic coronary artery disease (e.g., chest tightness, chest pain, palpitations, fatigue) or coronary artery disease requiring medical therapy; ⑤Severe bradycardia (heart rate \< 40 beats per minute \[bpm\]) with hypotension, dizziness, or syncope; patients with a history of arrhythmia should undergo cardiac evaluation;

           * Known active bacterial, viral, fungal, or other infection (excluding fungal infection of the nail bed), or major infection within 2 weeks prior to the first dose of study drug;

             * Moderate to severe hepatic impairment (Child-Pugh Class B or C); ⑧Active bleeding within 2 months prior to screening, or clear evidence of bleeding diathesis as judged by the investigator; ⑨Current pulmonary disease that impairs lung function, such as pulmonary fibrosis or drug-related pneumonitis, which is deemed intolerable by the investigator; ⑩Any psychiatric or cognitive disorder that may limit the patient's ability to understand, execute, or comply with the informed consent and study requirements;
3. Known active hepatitis C virus (HCV) infection; or other acquired or congenital immunodeficiency disorders, including but not limited to human immunodeficiency virus (HIV) infection;
4. All patients with central nervous system (CNS) involvement by lymphoma;
5. Diagnosis of or receiving treatment for another malignancy other than lymphoma, except for the following:

   ①Malignancy that has been treated with curative intent and with no known active disease for ≥ 5 years prior to enrollment;

   ②Adequately treated basal cell carcinoma of the skin (excluding melanoma) with no evidence of disease;

   ③Adequately treated carcinoma in situ of the cervix with no evidence of disease;
6. Known hypersensitivity to any study drug;
7. Pregnant or breastfeeding women;
8. History of stroke or intracranial hemorrhage within 6 months prior to enrollment;
9. Requirement for anticoagulation therapy with warfarin or equivalent vitamin K antagonists;
10. Requirement for long-term treatment with strong cytochrome P450 3A (CYP3A) inhibitors;
11. Receipt of live attenuated vaccine within 4 weeks prior to enrollment.

Conditions2

Interventions3

Related trials

• A PHASE I STUDY OF ALPS12 IN PATIENTS WITH EXTENSIVE STAGE SMALL CELL LUNG CANCER — Chugai Pharmaceutical
• A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure. — Australasian Leukaemia and Lymphoma Group
• A Phase-3-trial of Acalabrutinib, Obinutuzumab & Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk CLL — German CLL Study Group
• A Real-world Study of Obinutuzumab-based Therapy for Previously Untreated FL — Ruijin Hospital
• A Single Arm Study of Acalabrutinib Conbimed With Obinutuzumab in Chinese Patients With Previously Untreated CLL — The First Affiliated Hospital with Nanjing Medical University
• Obinutuzumab in Combination With Lenalidomide in Relapsed or Refractory Marginal Zone Lymphoma — Institute of Hematology & Blood Diseases Hospital, China
• Obinutuzumab, Zanubrutinib, and Lenalidomide in First-line Treatment of Mantle Cell Lymphoma — Institute of Hematology & Blood Diseases Hospital, China
• Phase II Study of Glofitamab With Venetoclax +/- Zanubrutinib in High-risk Mantle-cell Lymphoma — The Lymphoma Academic Research Organisation

Browse More Trials