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

Sponsor

Peking University People's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05369364

Collaborator

Beijing Hospital (Other), Navy General Hospital, Beijing (Other), Beijing Aerospace General Hospital (Other), Qilu Hospital of Shandong University (Other), Beijing Tongren Hospital (Other)

150

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenia	Drug: Zanubrutinib Drug: Dexamethasone	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Dec 30, 2025

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

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: Zanubrutinib Zanubrutinib 80mg qd po, 6 consecutive weeks Other Names: BTK inihibitor 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
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

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: Zanubrutinib

Zanubrutinib 80mg qd po, 6 consecutive weeks

Other Names:

BTK inihibitor

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

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

Outcome Measures

Primary Outcome Measures

Sustained response [12 months]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
Received first-line and second-line ITP-specific treatments (eg, steriods, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) ;
Current HIV infection or hepatitis B virus or hepatitis C virus infections;
Active infection;
Maligancy;
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);
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;
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.