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

Phase 2
Not yet recruiting
Conditions
Immune Thrombocytopenia
Interventions
Registration Number
NCT05369364
Lead Sponsor
Peking University People's Hospital
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).

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
150
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Zanubrutinib and HD-DXMZanubrutinibDexamethasone 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
Zanubrutinib and HD-DXMDexamethasoneDexamethasone 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
HD-DXMDexamethasoneDexamethasone 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)
Primary Outcome Measures
NameTimeMethod
Sustained response12 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
NameTimeMethod
Loss of response12 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)

Number of patients with bleeding12 months

Number of patients with bleeding complication ( WHO bleeding score).

Time to response (TTR)12 months

The time from starting treatment to time of achievement of CR or R

Durable response6 months

Platelet count ≥30 X 10\^9/L and at least doubling of the baseline count at 6 mo

Initial complete response1 month

Initial complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding.

Initial response1 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 adverse events12 months

Number of patients with adverse events

Duration of response (DOR)12 months

Duration of response at 12-month follow up

Early response1 week

Platelet count ≥30 X 10\^9/L and at least doubling baseline at 1 wk

Remission12 months

Platelet count \>100 X 10\^9/L at 12 month

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