Clinical Study of Orelabrutinib Combined With BG Regimen First-line Treatment of CLL/SLL

NCT05918276 | Not Yet Recruiting Phase 2

• 1 other identifier: NFEC-2023-202
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to investigate the treatment of navie CLL/SLL with orelabrutinib, bendamustine and obinutuzumab . The primary endpoint is the rate of CR and uMRD, and the second endpoints are survival time (OS and PFS) and toxicities.

Conditions

CLL/SLL

Keywords

Orelabrutinib; bendamustine; obintuzumab

Outcome Measures

Primary Outcomes (1)

• The rate of CR and uMRD

  The proportion of patients with CR and undetectable peripheral blood/bone marrow minimal residual disease in the end of combination therapy. Patients with CRi are counted as CR.

  Approximately 2 years.

Secondary Outcomes (4)

• The rate of CR/CRu and uMRD

  Approximately 2 years.

• The Rate of uMRD

  Approximately 2 years.

• PFS（progression-free survival）

  Up to 8 years.

• OS（overall survival）

  Up to 10 years.

Study Arms (1)

OBG

EXPERIMENTAL

Drug: Orelabrutinib and BG

Interventions

Orelabrutinib and BG DRUG

Drug: Orelabrutinib Orelabrutinib 200mg, po, qd，C2-C7. Twenty-eight days for a cycle. Drug: BG Bendamustin 70mg/m2, IV, d2\&d3 inC1, and then d1\&d2 inC2-6.Twenty-eight days for a cycle. Obintuzumab 100mg IV, d1, 900mg d2, 1000mg d8\&d15 in C1, and then 1000mg/m2 IV, d1 in C2-6. Twenty-eight days for a cycle.

Also known as: OBG

OBG

Eligibility Criteria

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

You may qualify if:

• years of age and older or between 18 and 65 years of age with severe illness (non-CLL/SLL associated CIRS ≥ 6);
• ECOG performance status (PS) level 0\~2；
• Expected survival is not less than 12 weeks;
• Chronic lymphocytic leukemia/small lymphocytic lymphoma diagnosed by flow cytometry or histopathology according to IWCLL2008 criteria, and CD20 positive;
• Meet at least 1 indication for treatment according to IWCLL2008 criteria or Chinese CLL/SLL guidelines 2022
• Enhanced computed tomography/magnetic resonance imaging (CT/MRI) to detect measurable lesions: at least one lymph node with a maximum axis of more than 1.5 cm and one measurable vertical dimension; for patients with chronic lymphocytic leukemia, only peripheral circulating lymphocyte count must be \> 5000/μL (or 5×10\^9/L);
• Have not received systematic treatment for CLL/SLL in the past;
• The main organs are functioning normally, the following criteria are met:
• Routine blood test standards should meet:
• Absolute neutrophil (ANC) ≥1.0×109/L, platelet (PLT) ≥30×109/L; unless bone marrow and hematopoietic insufficiency is confirmed to be due to CLL/SLL
• Biochemical examination should meet the following standards:
• TBIL\<2.0× ULN, CLL/SLL liver involvement or confirmed Gilbert syndrome (normal direct bilirubin), total bilirubia ≤ 3 times ULN;
• ALT and AST \<2.5×ULN (ALT and AST \<5×ULN for CLL/SLL liver involvement);
• Endogenous creatinine clearance ≥ 30 ml/min (Cockcroft-Gault formula).
• Women of childbearing age must have taken reliable contraceptive measures or have taken a pregnancy test (serum or urine) within 7 days prior to enrollment, have a negative result, and be willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the test drug. For men, consent to appropriate methods of contraception or surgical sterilization during the trial and 8 weeks after the last administration of the test drug must be agreed;

You may not qualify if:

• Patients with 17P- chromosome abnormalities or TP53 mutations;
• Current or previous biopsy pathology confirms conversion to Richter's syndrome;
• Have active and uncontrolled autoimmune cytopenias, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura;
• Patients with central nervous system invasion;
• Glucocorticoid therapy (at a dose equal to or greater than 20 mg/day of prednisone or equivalent) within 14 days prior to the first dose, excluding inhalation, topical medication, intra-articular medication, and prophylaxis before or after iodine contrast use; After discussion with the team leader, higher doses, longer steroid therapy may be allowed in the following cases:
• treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with CLL/SLL disease;
• Acute exacerbations due to short-term (within 14 days) use of inactive infections for diseases not associated with CLL/SLL (e.g., arthritis, asthma), including steroid dose adjustment required for adrenal insufficiency;
• Previous or concurrent uncured malignant tumors, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix and superficial bladder cancer;
• Suffering from the following cardiovascular diseases: grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval QTc \>480ms); According to NYHA standards, grade III.\~IV. cardiac insufficiency, or cardiac ultrasound showed left ventricular ejection fraction (LVEF) \< 50%;
• Coagulation dysfunction (INR\>1.5 or prothrombin time (PT) \>ULN+4 seconds or APTT \>1.5 ULN), bleeding tendency or receiving thrombolysis or anticoagulation therapy;
• Arteriovenous thrombotic events that occurred within 12 months before enrollment, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
• Known hereditary or acquired bleeding and thrombosis (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.);
• Have undergone major surgical procedures or developed severe traumatic injuries, fractures or ulcers within 4 weeks of enrollment;
• Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and intestinal obstruction;
• Active infection requiring antimicrobial therapy (such as antibacterial drugs and antiviral drugs, excluding chronic hepatitis B anti-hepatitis B treatment and antifungal treatment);

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (2)

The Central Hospital Of Wuan

Wuhan, Hubei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

MeSH Terms

Interventions

orelabrutinib

Study Officials

• Ru Feng, Master

  Nanfang Hospital, Southern Medical University

  STUDY CHAIR

Central Study Contacts

Ru Feng, Master

CONTACT

+8602061641615; ruth1626@hotmail.com

Xutao Guo, Dr.

CONTACT

+8602061641615; gxt827@126.com

Study Design

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

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: June 26, 2023
• Study Start: July 15, 2023
• Primary Completion: December 30, 2024
• Study Completion (Estimated): December 30, 2026
• Last Updated: June 26, 2023

Record last verified: 2023-06

Locations

CN (2)