- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06337474
An Clinical Study of CD19 CAR NK Cells for the Treatment of Refractory Primary Immune Thrombocytopenia
March 22, 2024 updated by: Lu Xuzhang, Changzhou No.2 People's Hospital
An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cell Injections for the Treatment of Refractory Primary Immune Thrombocytopenia
A single arm, open-label pilot study is designed to determine the safety and effectiveness of CD19 CAR NK cells (KN5501) in patients with refractory immune thrombocytopenia.
9 patients are planned to be enrolled in the dose-escalation trial (9×10^9 cells, 13.5×10^9 cells).
The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases.
The secondary objective is to evaluate evaluation of KN5501 for the treatment of refractory immune thrombocytopenia.
The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with refractory immune thrombocytopenia.
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
9
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Xuzhang Lu, Doctor
- Phone Number: +86-15295189493
- Email: Luxuzhang2008@163.com
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age: ≥ 18 years old and ≤ 65 years old, male or female, subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF);
- Diagnosis of systemic lupus erythematosus (SLE) (according to American Society of Hematology 2019 guidelines and International ITP Working Group);
- Platelet count is decreased in routine blood tests at least two consecutive times, with no obvious abnormalities in the morphology of blood cells on microscopic examination of peripheral blood smears;
- Spleen is not enlarged during screening;
- The morphology of bone marrow cells in subjects is characterized by increased or normal megakaryocytes with impaired maturation;
- Exclude other secondary thrombocytopenia: secondary thrombocytopenia due to autoimmune diseases, thyroid disorders, lymphoproliferative disorders, myelodysplastic syndromes (MDS), aplastic anemia (AA), various malignant blood disorders, neoplastic infiltrates, chronic liver disease, hypersplenism, common variable immunodeficiency disease (CVID), infections, vaccinations, etc.; thrombocytopenia; drug-induced thrombocytopenia; homozygous thrombocytopenia; thrombocytopenia during pregnancy; congenital thrombocytopenia and pseudothrombocytopenia. Thrombocytopenia due to consumption; drug-induced thrombocytopenia; isoimmune thrombocytopenia; thrombocytopenia in pregnancy; congenital thrombocytopenia and pseudothrombocytopenia;
- Subjects with refractory ITP who are refractory to first-line therapeutic agents, thrombopoietic agents in second-line therapy, and rituximab, or who have had ineffective splenectomies/postoperative recurrences, and who undergo diagnostic reassessment and remain diagnosed with ITP;
- Patients with refractory ITP: refractory to first-line therapeutic agents, thrombopoietic agents in second-line therapy, and rituximab; patients diagnosed with ITP despite unsuccessful splenectomy/postoperative recurrence on diagnostic reassessment
- ECOG score ≤ 1;
- Left ventricular ejection fraction (LVEF) ≥50% and no clinically significant pericardial effusion;
- ≥ 4 weeks after subjects received last dose treatment (Radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments);
- NRT, antimalarial monotherapy, antimalarials in combination with OCS and/or immunosuppressants, combination of OCS and/or immunosuppressants.
Exclusion Criteria:
- Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions;
- Subjects with active infection receiving intravenous (IV) antibiotic treatment, or received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR NK Cell (KN5501) infusion;
- Subjects with acquired and congenital immunodeficiency diseases;
- Subjects with grade III or IV heart failure (NYHA classification);
- History of epilepsy or other central nervous system (CNS) diseases;
- History of severe herpes infections such as herpes encephalitis, ocular herpes, or diffuse herpes;
History of other primary malignant tumors except:
a Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC) ; b Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer;
- Signs of herpes or varicella zoster virus infection (specifically varicella, zoster) within 12 weeks prior to screening; history of any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urinary, pulmonary, neurologic, dermatologic, psychiatric, and renal disease or other significant medical condition, other than lupus, that prevents administration of BIIB059 (as determined by the investigator)
- Females who are pregnant, lactating, or planning a pregnancy within six months;
- History or current diagnosis of clinically significant non-ITP-induced thrombocytopenia
- Subjects who have received other clinical trial treatment within 3 month;
- Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: anti-CD19 CAR NK cells
|
Patients will receive Fludarabine (25 mg/m2 per day) and Cyclophosphamide (1000mg/m2 per day) on day -3.
Doses of 9×10^9 cells, 13.5×10^9 anti-CD19 CAR NK cells (KN5501) will infused in each group using the dose-escalation strategy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Dose Limiting Toxicity (DLTs)
Time Frame: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
|
To characterize the Dose Limiting Toxicities (DLTs) of anti-CD19 CAR NK Cells for refractory immune thrombocytopenia
|
within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
|
Treatment Emergent Adverse Events (TEAEs)
Time Frame: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
|
To characterize the Treatment Emergent Adverse Events (TEAEs) of anti-CD19 CAR NK Cells for refractory immune thrombocytopenia
|
within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate of subjects
Time Frame: Time Frame: 2, 4, 8, 12, 16, 24, 28, 40 and 52 weeks after first infusion
|
Objective Response is assessed according to definitions of International ITP Working Group.
Objective Response Rate is defined as proportion of patients with PLT content.
|
Time Frame: 2, 4, 8, 12, 16, 24, 28, 40 and 52 weeks after first infusion
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
March 30, 2024
Primary Completion (Estimated)
March 30, 2025
Study Completion (Estimated)
March 30, 2026
Study Registration Dates
First Submitted
March 19, 2024
First Submitted That Met QC Criteria
March 22, 2024
First Posted (Actual)
March 29, 2024
Study Record Updates
Last Update Posted (Actual)
March 29, 2024
Last Update Submitted That Met QC Criteria
March 22, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
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
- Cytopenia
- Purpura, Thrombocytopenic, Idiopathic
- Thrombocytopenia
Other Study ID Numbers
- [2023]YLJSA089
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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