Clinical trial NCT05320081: Camrelizumab Combined With CD30 CAR-T in the Treatment of Relapsed/Refractory CD30+ Lymphoma
Official title: Camrelizumab Combined With CD30 CAR-T in the Treatment of Relapsed/Refractory CD30+ Lymphoma: a Single-arm, Open-label Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma
Relapse/Recurrence
Keywords: CD30 positive
Lead sponsor: Huazhong University of Science and Technology
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Nanchang University
First posted: 2022-04-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: overall response rate
timeFrame: up to 3 months after CAR-T cell infusion
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: up to 90 days
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 24 months
measure: Duration of remission (DOR)
timeFrame: 24 months
measure: Progression-free Survival (PFS)
timeFrame: 24 months
measure: Time to Remission (TTR).
timeFrame: 12 months
Other outcomes:
measure: The copy number of CD30 CAR-T cells
timeFrame: 12 months
Locations:
city: Wuhan
country: China
facility: Department of Hematology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
affiliation: Huazhong University of Science and Technology
name: Jianfeng Zhou
role: PRINCIPAL_INVESTIGATOR
References: