Camrelizumab Combined With CD30 CAR-T in the Treatment of Relapsed/Refractory CD30+ Lymphoma

NCT ID: NCT05320081

Last Updated: 2022-04-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-30
• Study Completion Date: 2024-06-30

Brief Summary

The is a phase II, single-arm, open-label clinical study assessing the efficacy and safety of Camrelizumab combined with CD30 CAR-T in the treatment of r/r CD30+ lymphoma. Plan to recruit 30 subjects with r/r CD30+ lymphoma。

Detailed Description

This study intends to combine CD30 CAR-T (provided by Wuhan Bio-Raid Biotechnology Co., Ltd) and Camrelizumab (provided by Jiangsu Hengrui Pharmaceutical Co., Ltd.) to treat r/r CD30+ lymphoma, to observe the safety and effectiveness of the combined treatment, and to study the effect of PD-1 antibody on the pharmacokinetics and pharmacodynamics of CAR-T. Obtain a better treatment plan and provide a new strategy for the treatment of clinically r/r CD30+ lymphoma.

Conditions

Lymphoma; Relapse/Recurrence

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Camrelizumab combined with CD30 CAR-T

This study have only one arm that is Camrelizumab combined with CD30 CAR-T experimental arm.

Group Type: EXPERIMENTAL

CD30 CAR-T

Intervention Type: BIOLOGICAL

Subjects need to complete a series of checks before reinfusion of CD30 CAR-T cells as baseline information for subjects after non-myeloablative pretreatment. The subject was reinfused with CD30 CAR-T cells (10±3)×10^6/kg on the 0th day of the first dosing cycle (the investigator decided the specific reinfusion dose based on the subject's own/disease conditions and preparation conditions in vitro ), concurrent oxygen inhalation and monitoring (ECG, blood pressure and blood oxygen monitoring). The reinfusion was completed in about 30 minutes, and the tube was flushed with saline.

Note: CAR-T cell infusion and reinfusion dose are based on the subject's condition.

Camrelizumab

Intervention Type: DRUG

Received Camrelizumab treatment on the 15th day after CAR-T cell reinfusion, and then received Camrelizumab treatment every 2 weeks.

Interventions

CD30 CAR-T

Subjects need to complete a series of checks before reinfusion of CD30 CAR-T cells as baseline information for subjects after non-myeloablative pretreatment. The subject was reinfused with CD30 CAR-T cells (10±3)×10^6/kg on the 0th day of the first dosing cycle (the investigator decided the specific reinfusion dose based on the subject's own/disease conditions and preparation conditions in vitro ), concurrent oxygen inhalation and monitoring (ECG, blood pressure and blood oxygen monitoring). The reinfusion was completed in about 30 minutes, and the tube was flushed with saline.

Note: CAR-T cell infusion and reinfusion dose are based on the subject's condition.

Intervention Type: BIOLOGICAL

Camrelizumab

Received Camrelizumab treatment on the 15th day after CAR-T cell reinfusion, and then received Camrelizumab treatment every 2 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• age≥18 years and ≤70 years，female and male；
• ECOG performance status 0-2；
• Histological or flow cytometry confirmed CD30+ lymphoma [according to WHO2008 diagnostic standard]
• Patients with CD30+ lymphoma relapsed after ≥2 lines of systemic treatment (the disease progresses after treatment remission) or refractory ( failed to obtain CR after previous systemic treatment)；
• The patient did not receive any chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) and other anti-cancer treatments within 4 weeks before enrollment, and the treatment-related toxicity has recovered to ≤ Grade 1 (except for alopecia) 4 weeks before enrollment；
• At least 1 evaluable or measurable lesion can be measured according to the LYRIC 2016 evaluation criteria for malignant lymphoma ；
• Sufficient organ and bone marrow function, no serious abnormalities neither in hematopoietic function nor in heart, lung, liver, and kidney functions, and no immune deficiencies;

1. The absolute value of neutrophils is ≥1.5×109/L (for patients with bone marrow invasion ≥1.0×109/L);

2. Platelets ≥75×109/L (patients with bone marrow invasion ≥50×109/L);

3. Hemoglobin ≥9 g/dL;

4. Serum creatinine ≤ 1.5× the upper limit of normal (ULN), or creatinine clearance ≥40 mL/min (estimated based on the Cockcroft-Gault formula);

5. Serum total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN ( liver invasion);.

6. f) Aspartate aminotransferase、Alanine Aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN ( liver invasion);

7. Coagulation function: International Normalized Ratio (INR) ≤ 1.5 × ULN; Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (the PT and APTT should be within the expected range of anticoagulant therapy at the time of screening if the subject is receiving anticoagulant therapy,).

8. Thyroid-stimulating hormone (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) are within ±10% of the normal value.

9. Left ventricular ejection fraction (LVEF) ≥ 50%, no serious malignant arrhythmia;

• The estimated survival time ≥6 months;
• Sufficient understanding and voluntarily to sign the informed consent form;
• Patients with fertility must be willing to be able to use reliable contraceptive measures during the clinical study and within 12 months after the last administration

Exclusion Criteria

• Lymphoma associated hemophagocytic syndrome;
• Patients diagnosed as primary cutaneous anaplastic large cell lymphoma （ALCL） (patients can be enrolled if ALCL is transformed from other organ involvement);
• Patients with malignant T cells involving bone marrow or peripheral blood;
• Suffered from other malignant tumors in the past 5 years, except for for skin basal cell carcinoma, skin squamous cell carcinoma, breast carcinoma in situ and cervical carcinoma in situ undergoing the radical treatment
• Received CAR-T therapy or other genetically modified cell therapy before screening
• Received other treatments that affect the collection of T cells for when enrolled or within 4 weeks before enrollment;
• Suffer from active autoimmune diseases that require systemic treatment in the past two years (hormone replacement therapy is not considered as systemic treatment, such as type I diabetes, hypothyroidism that requires only thyroxine replacement therapy, patients with low adrenal function or hypopituitarism who need only physiological doses of glucocorticoid replacement therapy);
• Patients with uncontrolled infectious diseases, active viral hepatitis, tuberculosis, and HIV-infected ;
• Known to be allergic to ampicillin, antibodies, cytokines, anti-PD-1/PD-L1 antibodies or pharmaceutical excipients; or have severe allergic reactions to other monoclonal antibodies;
• Previous use of immunosuppressive drugs within 14 days before the first use of the drug, excluding nasal sprays and inhaled corticosteroids or physiological doses of systemic steroid hormones (ie not more than 10 mg/day prednisolone or equivalent physiological doses of other corticosteroids);
• long-term use of systemic hormones (dose equivalent to >10mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects using inhaled or topical corticosteroids can be enrolled;
• Suffer from uncontrolled comorbidities, including but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer or bleeding disorders.
• With history of interstitial lung disease or non-infectious pneumonia. Subjects who have previously had drug-induced or radioactive non-infectious pneumonia but asymptomatic are allowed to enroll.
• Patients have other conditions that are not suitable for enrollment according to the judgment of the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Jianfeng Zhou

Director of the Division of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianfeng Zhou

Role: PRINCIPAL_INVESTIGATOR

Huazhong University of Science and Technology

Locations

Department of Hematology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status: RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianfeng Zhou, MD, PhD

Role: CONTACT

jfzhou@tjh.tjmu.edu.cn

86-13627284963

Xiaoxi Zhou, MD, PhD

Role: CONTACT

cello316@tjh.tjmu.edu.cn

86-027-83662686

Facility Contacts

Jianfeng Zhou, PhD

Role: primary

jfzhou@tjh.tjmu.edu.cn

86-13627284963

Fei Li, PhD

Role: primary

yx021021@sina.com

13970038386

Other Identifiers

MA-ML-Ⅱ-001

Identifier Type: -

Identifier Source: org_study_id