TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies

NCT04915482 | Recruiting Phase 2

• 1 other identifier: IIT2020034
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, open-label, nonrandomized, multicenter clinical trial aims at comparing the efficacy and safety of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody vs. the best available therapy（BAT）in adult immune thrombocytopenia with autoantibodies failed (due to intolerance or resistance) to first-line treatment.

Conditions

Immune Thrombocytopenia (ITP); Autoantibodies; Evan Syndrome; Connective Tissue Diseases

Outcome Measures

Primary Outcomes (1)

• Platelet response

  At weeks 4-24, the proportion of subjects with platelet count (PLT) ≥30×10\^9/L and at least 2 times the baseline value in 4 out of 6 consecutive tests (at least 1 week interval between each test).

  From the start of study treatment (Day 1) up to the end of week 24

Secondary Outcomes (13)

• Platelet response

  From the start of study treatment (Day 1) up to the end of week 4, 8 and 12

• Platelet response

  From the start of study treatment (Day 1) up to the end of week 4, 8 and 12

• Time to platelet response

  From the start of study treatment (Day 1) up to the end of week 24

• Duration of platelet response

  From the start of study treatment (Day 1) up to the end of week 24

• Bleeding score

  From the start of study treatment (Day 1) up to the end of week 24

Other Outcomes (1)

• Incidence of Toxicity

  From the start of study treatment (Day 1) up to the end of week 24

Study Arms (2)

Combined use of TPO-RAs with low-dose anti-CD20 antibody

EXPERIMENTAL

The starting dose of eltrombopag is 50-75mg once daily. The starting dose of hetrombopag is 5.0-7.5mg once daily. The starting dose of avatrombopag is 20-40mg once daily. Prior to or within 2 weeks after initiation of TPO-RAs therapy, a single dose of Rituximab at 375mg/m2 or divided doses of Rituximab at 100mg once a week for 2-4 weeks, or a single dose of ortuzumab at 1000mg can be administered.. The dosage will be adjusted according to the results of laboratory examinations and patient tolerance.

Drug: Combined use of TPO-RAs with low-dose anti-CD20 antibody

The best available therapy other than combined use of TPO-RAs with low-dose anti-CD20 antibody

ACTIVE COMPARATOR

The best available therapy except for combined use of TPO-RAs with low-dose anti-CD20 antibody includes but not limited to glucocorticoids, intravenous immunoglobulin, recombinant human thrombopoietin, TPO receptor agonists monotherapy, rituximab monotherapy, immunosuppressants, etc., and the researchers will adjust the treatment plan at any time according to the patient's condition.

Drug: The best available therapy

Interventions

Combined use of TPO-RAs with low-dose anti-CD20 antibody DRUG

Experimental: Combined use of TPO-RAs with low-dose anti-CD20 antibody The starting dose of eltrombopag is 50-75mg once daily. The starting dose of hetrombopag is 5.0-7.5mg once daily. The starting dose of avatrombopag is 20-40mg once daily. Prior to or within 2 weeks after initiation of TPO-RAs therapy, a single dose of Rituximab at 375mg/m2 or divided doses of Rituximab at 100mg once a week for 2-4 weeks, or a single dose of ortuzumab at 1000mg can be administered.. The dosage will be adjusted according to the results of laboratory examinations and patient tolerance.

Combined use of TPO-RAs with low-dose anti-CD20 antibody

The best available therapy DRUG

The best available therapy except for combined use of TPO-RAs with low-dose anti-CD20 antibody includes but not limited to glucocorticoids, intravenous immunoglobulin, recombinant human thrombopoietin, TPO receptor agonists monotherapy, rituximab monotherapy, immunosuppressants, etc., and the researchers will adjust the treatment plan at any time according to the patient's condition.

The best available therapy other than combined use of TPO-RAs with low-dose anti-CD20 antibody

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients have provided written informed consent prior to enrollment.
• years old.
• Diagnosed as ITP secondary to connective tissue diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis), primary ITP with positive antinuclear antibody but not up to the diagnostic criteria of connective tissue diseases, primary Evans syndrome, Evans syndrome secondary to connective tissue diseases, and primary ITP with positive Coomb's test but not up to the diagnostic criteria of Evans syndrome.
• Platelet count\<30 ×10\^9/L at screening.
• Patients who have received at least one first-line treatment of ITP (glucocorticoid and / or intravenous immunoglobulin) in the past, failed (poor efficacy, or failure to maintain efficacy, or relapse), or had contraindications, intolerance, or refusal of first-line treatment.
• Treatment for ITP (including but not limited to glucocorticoids, recombinant human thrombopoietin (rTPO)) must be completed before enrollment, or the dose must be stable or in a phase of reduction within 2 weeks before enrollment. Immunosuppressants (including but not limited to azathioprine, danazol, cyclosporine A, mycophenolate mofetil) must be finished before entering the group, or the dose must be stable or in the reduction period within 3 months before entering the group.
• Effective contraceptive measures will be taken during the clinical trial.

You may not qualify if:

• Thrombocytopenia secondary to thyroid disease.
• Patients with any prior history of arterial or venous thrombosis, and with any of the following risk factors: cancer, Factor V Leiden, ATIII deficiency, and antiphospholipid syndrome.
• Those who had received anti-CD20 monoclonal antibody within 6 months or who had previously failed to respond to low-dose anti-CD20 monoclonal antibody.
• Patients who had failed to respond to the previous use of eltrombopag 75 mg once a day, hetrombopag 7.5mg once a day or avatrombopag 40mg once a day for more than 4 weeks.
• Patients who have received splenectomy within one year or have splenectomy plan within one year.
• Patients with lupus encephalopathy or lupus nephritis.
• Patients with cataract.
• Patients with infectious fever (including but not limited to pulmonary infection) within 1 month or with active infection during screening.
• Existing hepatitis B virus, hepatitis C virus replication or HIV infection.
• Patients with agranulocytosis (ANC \<1× 10\^9/L), or moderate and severe anemia (HGB \< 90g/L). For patients with Evans syndrome, patients with HGB\< 60g/L will be excluded.
• Severe liver dysfunction (alanine aminotransferase or glutamic oxaloacetic transaminase \> 3×ULN), or bilirubin level \> 2×ULN except patients with Evans syndrome.
• Patients with severe cardiac or pulmonary dysfunction.
• Severe renal damage (creatinine clearance \< 50 ml/min).
• There were surgical planners during the study.
• History of psychiatric disorder.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Evans Syndrome; Connective Tissue Diseases

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Skin and Connective Tissue Diseases

Study Officials

• Lei Zhang, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

• Rongfeng Fu

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rongfeng Fu, MD

CONTACT

+862223909009; furongfeng@ihcams.ac.cn

Lei Zhang, MD

CONTACT

+862223909240; zhanglei1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: June 7, 2021
• Study Start: June 6, 2021
• Primary Completion: January 31, 2025
• Study Completion: February 28, 2025
• Last Updated: July 3, 2024

Record last verified: 2024-03

Locations

CN (1)