Multi-target Drugs Sequential Combination Therapy in Adults Patients With Newly Diagnosed Primary Immune Thrombocytopenia

Efficacy and Safety of Multi-Target Drugs Sequential Combination Therapy in Adults Patients With Newly Diagnosed Primary Immune Thrombocytopenia: A Prospective, Single-arm, Multicenter, Exploratory Trial

This prospective, single-arm, multicenter, exploratory study will enroll 38 adults patients with newly diagnosed primary immune thrombocytopenia (ITP). Patients will receive standard-dose corticosteroids plus a thrombopoietin receptor agonist (TPO-RA) as initial therapy During the core treatment phase (Weeks 1-12). Corticosteroids will be tapered and discontinued within 8 weeks, whereas TPO-RA treatment will continue for 12 weeks. For patients with treatment failure( defined as platelet count < 30 × 10^9/L or less than 2-fold increase of baseline platelet count or bleeding) ,a sequential multitarget combination strategy will be explored in subsequent treatment phases. Specifically, patients with treatment failure after 2 weeks of initial therapy (Weeks 3-12), will receive the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody（mAb） as sequential combination therapy.

During the core treatment follow-up phase (24 weeks), patients with treatment failure will enter the exploratory treatment phase (Weeks 13-36) .

Patients who received multi-target drug therapy during the core treatment period will switch to an alternative TPO-RA with cross-administered rituximab and anti-CD38 mAb, while those who did not will receive sequential rituximab or anti-CD38 mAb.

Finally, patients will enter the safety follow up period (4 weeks, weeks 37-40).

The study will be conducted in three phases.

Phase 1. Core treatment phase includes initial treatment and sequential combination therapy (12 weeks, weeks 1-12):

Patients will receive standard-dose methylprednisolone or prednisone in combination with a thrombopoietin receptor agonist (TPO-RA) as initial therapy.Corticosteroids will be tapered and discontinued within 8 weeks; tapering will begin immediately in patients who achieve complete response (CR) and will also be initiated after 4 weeks in patients who do not achieve response (R). TPO-RA therapy will continue for 12 weeks, with dose adjustments made according to the approved prescribing information. Patients with treatment failure( defined as platelet count < 30 × 10^9/L or less than 2-fold increase of baseline platelet count or bleeding) after 2 weeks of initial therapy (Weeks 3-12) will receive the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody as sequential combination therapy.

Phase 2. Core-treatment follow-up and exploratory treatment phase (24weeks, weeks 13-36):

During the core treatment follow-up phase, patients with treatment failure will enter the exploratory treatment phase. Patients who did not receive rituximab or anti-CD38 monoclonal antibody during the core treatment phase will receive a switched TPO-RA combined with either rituximab or anti-CD38 monoclonal antibody, whereas patients who received either rituximab or anti-CD38 monoclonal antibody during the core phase will receive a switched TPO-RA combined with cross-administered rituximab and anti-CD38 monoclonal antibody.TPO-RA therapy will also continue for 12 weeks.

Phase3. Safety follow-up phase (4weeks,weeks 37-40).

Rescue therapy includes, but is not limited to, intravenous immunoglobulin (IVIG), platelet transfusion, and vindesine. A switch to another thrombopoietin receptor agonist (TPO-RA) will be considered rescue therapy during the core treatment period. Administration of recombinant human thrombopoietin (rhTPO) will also be considered rescue therapy.

Inclusion Criteria:

1. Age ≥18 years.
2. Confirmed newly diagnosed primary ITP with a platelet count <30 × 10^9/L.
3. No prior ITP-related treatment before enrollment, except for standard-dose corticosteroids and/or IVIG for ≤5 days.
4. Able to understand the study and provide signed informed consent.-

Exclusion Criteria:

1. Use of corticosteroids or immunosuppressants for a non-ITP condition within 3 months.

2. Contraindication to corticosteroid therapy.

3. Arterial or venous thromboembolic event within 3 months.

4. Pregnant or breastfeeding women.

5. Current treatment with another investigational drug.

6. Any other medical history or condition that, in the investigator's judgment, makes the participant unsuitable for the study.

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