A Study of Orelabrutinib in CLL/SLL Patients Who Are Slowly Responding to Ibrutinib

This is a single arm, multi-center study to evaluate the efficacy and safety of orelabrutinib for Chronic lymphocytic lymphoma（CLL)/small lymphocytic lymphoma (SLL) patients who are slowly responding to Ibrutinib switched to Orelabrutinib.

Study Overview

• Status: Recruiting
• Conditions: CLL/SLL
• Intervention / Treatment: Drug: orelabrutinib

Detailed Description

The eligible CLL/SLL patients who are slowly responding to Ibrutinib will be switched to Orelabrutinib treatment. The patients will receive Orelabrutinib 150mg oral daily (28 days/cycle) for up to 2 year or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shenmiao Yang; Phone Number: +8601088326666; Email: yangshenmiao@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Shenmiao Yang, MD
    • Beijing, Beijing, China, 100044
      • Not yet recruiting
      • Department of Hematology, Peking University People's Hospital
      • Contact: Xiaojun Huang; Phone Number: +8601088326666; Email: xjhrm@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years old， male or female
• Diagnosed as CLL/SLL based on iwCLL2018 criteria
• Enhanced computed tomography/magnetic resonance imaging (CT/MRI) detection had measurable lesions: at least one lymph node had a maximum axis of more than 1.5 cm and had a measurable vertical dimension
• ECOG score 0-2
• Slowly responding to ibrutinib is defined as: patients only achieve SD after 3 cycles of ibrutinib treatment
• Life expectancy ≥6 months
• Adequate bone marrow reserve and adequate organ function
• Participant or his/her legal agent must be willing to sign a written informed consent document.

Exclusion Criteria:

• Evidence of active Richter's transformation or any evidence of disease progression on ibrutinib therapy.
• CNS involvement by CLL
• Present or prior history of other malignant neoplasms, unless radical treatment has been performed and there is no evidence of recurrence or metastasis in the last 5 years
• Uncontrolled or significant cardiovascular disease
• Active hemorrhage within 2 months prior screening
• Cerebral ischemic stroke or bleeding within 6 months prior screening
• Other surgery history within 6 weeks prior screening
• Uncontrolled active systemic fungal, bacterial, virus or other microbe infection, or intravenous injection of antibiotics needed
• Anti-tumor corticosteroids treatment 1 week prior orelabrutinib and anti-tumor herbal medicine treatment within 4 weeks prior screening
• Activated or uncontrolled hepatitis virus B infection (HBsAg positive with/or HBc Ab positive and HBV-DNA titration positive), HCV-RNA positive, HIV positive.
• Accepted live vaccine or immunization within 4 weeks prior screening
• Medium / strong inhibition or induction of cytochrome P450 CYP3A is needed.
• Allergy to orelabrutinib or the subsidiary (or supplementary) material (Hydroxypropyl methylcellulose acetate succinate, mannitol, cross-linked sodium carboxymethylcellulose, hydroxypropyl cellulose, silica and magnesium stearate)
• Obvious gastro-bowel disease which may influence the intaking, transportation or absorption of the drug, or total gastrectomy.
• Pregnant or breeding women, or women of childbearing age who are unwilling to take contraceptive measures during the whole study period and within 180 days after the last administration of the study drug; non surgically sterilized men who are unwilling to take contraceptive measures during the whole study period and within 180 days of the last administration of the study drug.
• Potentially life-threatening situation, or severe organ dysfunction, or situations the researchers think not suitable for the trial
• Any mental or cognitive impairment which may limit the understanding and implementation of informed consent or the compliance with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: orelabrutinib; CLL/SLL patients who are slowly responding to ibrutinib are switched to orelabrutinib.	Drug: orelabrutinib; Orelabrutinib 150mg po qd d1-28, up to 2 years or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at cycle 3 after switched to orelabrutinib	Overall response rate is defined as the proportion of patients with a best response of CR/CRi and PR/PR-L	at cycle 3 (28 days/cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR	The time from the first assessment of CR/CRi or PR/PR-L to progressive disease or death (due to any cause).	Up to 2 years
PFS	Progression-free survival is calculated from the date of start of therapy until the date of first documented progress or death due to any cause.	Up to 2 years
OS	Overall survival is defined as the duration from start of treatment to time of death.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BTK occupancy	The percentage of orelabrutinib/ibrutinib-bound BTK	Before taking orelabrutinib and take orelabrutinib for 3-6 cycles

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Shenmiao Yang, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): August 28, 2024
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: August 1, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: Slowly responding switch IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No