The Combination of Zanubrutinib and High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia

The Combination of Oral Zanubrutinib and High-dose Dexamethasone vs High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia: A Multicenter, Randomized, Open-label Trial

Randomized, open-label, multicenter study to compare the efficacy and safety of zanubrutinib plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Dexamethasone; Drug: Zanubrutinib

Detailed Description

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of patients with ITP in China. Patients were randomized to Zanubrutinib + high-dose dexamethasone and high-dose dexamethasone monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed newly-diagnosed, treatment-naive ITP;
2. Platelet counts <30×10^9/L ;
3. Platelet counts < 50×10^9/L and significant bleeding symptoms (WHO bleeding scale 2 or above);
4. Willing and able to sign written informed consent.

Exclusion Criteria:

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
2. Received first-line and second-line ITP-specific treatments (eg, steriods, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) ;
3. Current HIV infection or hepatitis B virus or hepatitis C virus infections;
4. Active infection;
5. Maligancy;
6. Severe medical condition (lung, hepatic or renal disorder) other than chronic ITP. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia);
7. Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period; a history of clinically significant adverse reactions to previous corticosteroid therapy;
8. Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib and HD-DXM; Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 10) and Zanubrutinib 80mg qd po, 6 consecutive weeks	Drug: Dexamethasone; Dexamethasone, iv, 40 mg/d, for 4 days (The 4-day course of dexamethasone was repeated in the case of lack of response by day 10); Other Names: HD-DXM; Drug: Zanubrutinib; Zanubrutinib 80mg qd po, 6 consecutive weeks; Other Names: BTK inihibitor
Active Comparator: HD-DXM; Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone was repeated in the case of lack of response by day 10)	Drug: Dexamethasone; Dexamethasone, iv, 40 mg/d, for 4 days (The 4-day course of dexamethasone was repeated in the case of lack of response by day 10); Other Names: HD-DXM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained response	The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 12-month follow-up	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events	Number of patients with adverse events	12 months
Duration of response (DOR)	Duration of response at 12-month follow up	12 months
Initial complete response	Initial complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding.	1 month
Initial response	Initial response (R) as platelet count more than 30,000 per cubic millimeter and at least 2-fold increase of the baseline count and absence of bleeding.	1 month
Number of patients with bleeding	Number of patients with bleeding complication ( WHO bleeding score).	12 months
Time to response (TTR)	The time from starting treatment to time of achievement of CR or R	12 months
Loss of response	Platelet counts below 100 x 109/L or bleeding (from CR) or platelet counts below 30 x 109/L, less than 2-fold increase of baseline platelet count or bleeding (from R)	12 month
Durable response	Platelet count ≥30 X 10^9/L and at least doubling of the baseline count at 6 mo	6 months
Early response	Platelet count ≥30 X 10^9/L and at least doubling baseline at 1 wk	1 week
Remission	Platelet count >100 X 10^9/L at 12 month	12 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Qilu Hospital of Shandong University; Beijing Tongren Hospital; Beijing Hospital; Navy General Hospital, Beijing; Beijing Aerospace General Hospital
• Investigators: Principal Investigator: Xiaohui Zhang, MD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): December 30, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: BTK inhibitor; High-dose Dexamethasone
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Dexamethasone; Zanubrutinib
• Other Study ID Numbers: HDDXM-Zan-ITP

Drug and device information, study documents

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