Trial Title:
Safety and Efficacy of Anti-CD20/CD30 CAR-T Cells in Subjects with Relapsed/Refractory Lymphoma
NCT ID:
NCT06532643
Condition:
Relapsed/Refractory Lymphoma
Conditions: Official terms:
Lymphoma
Cyclophosphamide
Fludarabine
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Genetic
Intervention name:
anti-CD20/CD30-CAR-T cells
Description:
Each subject will be infused with single dose of anti-CD20/CD30-CAR-T cells. A classic
"3+3" dose escalation will be employed.
Arm group label:
Anti-CD20/CD30-CAR-T Cell Therapy
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Fludarabine will be given at a dose of 25 mg/m2/day intravenously (IV) for 3 days prior
to the infusion of anti-CD20/CD30-CAR-T cells.
Arm group label:
Anti-CD20/CD30-CAR-T Cell Therapy
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Cyclophosphamide will be given at a dose of 250 mg/m2/day intravenously (IV) for 3 days
prior to the infusion of anti-CD20/CD30-CAR-T cells.
Arm group label:
Anti-CD20/CD30-CAR-T Cell Therapy
Summary:
This study is an exploratory clinical trial of a single-center, open-label, single-dose
treatment of anti-CD20/CD30-CAR-T cells in subjects with relapsed/refractory lymphoma.
Detailed description:
The study will enroll subjects with CD20 and CD30-positive lymphoma, CD20-positive
lymphoma, or CD30-positive Hodgkin lymphoma. Subjects will receive a single infusion of
anti-CD20/CD30-CAR-T cells after screening, PBMC collection, and lymphodepleting
chemotherapy. Toxicity will be assessed according to the Common Terminology Criteria for
Adverse Events (CTCAE, version 5.0) from the National Cancer Institute. Safety of
anti-CD20/CD30-CAR-T cell therapy will be evaluated through laboratory tests, including
12-lead electrocardiograms, vital sign checks, etc. Additionally, blood samples will be
collected from subjects to study cellular pharmacokinetics and explore the effects of
cell therapy on ferritin, C-reactive protein, and related cytokines.
Criteria for eligibility:
Criteria:
Inclusion Criteria
- Patients must meet all of the following criteria to be eligible for the study:
1. Voluntarily participate in the clinical study. The individual or the legal
guardian fully understands the study, sign the informed consent form (ICF), and
is willing and able to follow and complete all trial procedures.
2. Age ≥ 14 years and < 70 years.
3. Subjects with refractory or relapsed disease after current standard treatments
(including allogeneic or autologous hematopoietic stem cell transplantation)
who are not suitable for other treatment options, such as a second stem cell
transplant. The definitions of relapsed/refractory lymphoma include one of the
following situations:
1. No response to first-line treatment (primary refractory disease, excluding
participants intolerant to first-line treatments).
- Disease progression (PD) as assessed after first-line treatment.
- Best efficacy of first-line treatment (e.g., 4 cycles of RCHOP) as
stable disease (SD), with the duration of SD not exceeding 6 months
after the last dose.
2. No response to second-line or more treatments.
- PD being the best response to the most recent treatment.
- Best efficacy of the last line of treatment as SD after at least 2
cycles, with the duration of SD not exceeding 6 months after the last
dose.
3. Refractory after autologous stem cell transplant (ASCT).
- Disease progression or relapse ≤ 12 months post-ASCT (relapsed
patients must have biopsy-proven relapse).
- If salvage treatment is administered after ASCT, the subjects must
not have had a response or relapse after the last line of treatment.
- Relapsed or refractory disease after two or more lines of systemic
treatment.
4. Lymphoma patients must have target antigens meeting the following criteria:
1. CD20/CD30 double-positive expressing lymphoma.
2. Relapse after receiving anti-CD19-CAR-T cell therapy, with CD20 positive
lymphoma.
3. CD20 positive lymphoma that has not previously received anti-CD19-CAR-T
cell therapy.
4. CD30 positive Hodgkin lymphoma.
5. Subtypes of lymphoma included for enrollment are as follows:
1. DLBCL-NOS (diffuse large B-cell Lymphoma, not otherwise specified)
2. Primary mediastinal B-cell lymphoma (PMBCL)
3. Transformed follicular lymphoma (TFL), previously treated for follicular
lymphoma and then transformed to refractory DLBCL
4. Mantle cell lymphoma
5. High-grade B-cell lymphoma
6. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
7. Hodgkin lymphoma (HL)
6. ECOG performance status ≤ 2.
7. Expected survival of at least 12 weeks.
8. Adequate venous access (for apheresis) and no other contraindications for blood
cell separation.
9. Laboratory tests during screening must meet the following requirements, and the
hematological assessment must not have received cell growth factors within 7
days (long-acting colony-stimulating factors (G-CSF/PEG-CSF) require a 2-week
interval) or platelet transfusions:
1. Absolute neutrophil count ≥ 1.0×10^9/L.
2. Hemoglobin ≥ 60 g/L (without red blood cell transfusion in the last 7
days).
3. Platelets ≥ 50×10^9/L (unrestricted for CLL indications).
4. Total bilirubin ≤ 1.5× the upper limit of normal (ULN); or total bilirubin
≤ 3× ULN when the tumor invades liver tissue.
5. Aspartate transaminase (AST), alanine transaminase (ALT) ≤ 2.5×ULN, with
AST/ALT ≤ 5×ULN when the tumor invades liver tissue.
6. Creatinine < 1.5× ULN and estimated creatinine clearance ≥ 60 mL/min.
10. Ejection fraction ≥ 45%, with echocardiogram (ECHO) confirming no pericardial
effusion (excluding small or physiological amounts), and electrocardiogram
results with no clinical significance.
11. Baseline oxygen saturation > 92% without supplemental oxygen.
12. Women of childbearing potential must have a negative serum or urine pregnancy
test result (women who have undergone surgical sterilization or have been
postmenopausal for at least 2 years are not considered of childbearing
potential).
Exclusion Criteria:
- Subjects are not eligible to participate in this study if they meet any of the
following criteria:
1. MRI of the brain shows evidence of central nervous system lymphoma; active
primary central nervous system DLBL, unless central nervous system involvement
has been effectively treated (i.e., participant is asymptomatic), and there has
been more than a 4-week gap since local treatment.
2. Active central nervous system diseases, such as epilepsy, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar diseases, or any autoimmune diseases
with central nervous system involvement.
3. History of or concurrent diagnosis of malignancies other than CD19+
malignancies.
4. Clinically significant heart disease or arrhythmias that cannot be controlled
with medication.
5. Presence or suspicion of fungal, bacterial, viral, or other infections that are
uncontrolled or require intravenous antibiotics for treatment; uncomplicated
urinary tract infections and uncomplicated bacterial pharyngitis are allowed.
6. Positive for hepatitis B (HBsAg positive and HBV DNA >1000 copies/mL) and
hepatitis C (positive for HCV antibodies); syphilis or human immunodeficiency
virus (HIV) infection.
7. Presence of any indwelling catheter or drainage tube (such as percutaneous
nephrostomy, indwelling Foley catheter, bile drainage tube, or
pleural/peritoneal/pericardial catheter); use of specialized central venous
access devices like Port-A-Cath® or Hickman® catheters is allowed.
8. History of using any of the following medications:
1. Lenalidomide within 1 day before the apheresis.
2. Idelalisib (oral PI3Kδ inhibitor) within 2 days before the apheresis.
3. Short-acting targeted therapy (like tyrosine kinase inhibitors) within 72
hours before the apheresis.
4. Venetoclax (BCL-2 inhibitor) within 4 days before the apheresis.
5. Long-acting growth factors (like pegylated filgrastim) within 14 days
before the apheresis, or short-acting growth factors or mobilization
agents (like G-CSF/filgrastim, plerixafor) within 5 days before the
apheresis.
6. Pharmacological doses of corticosteroids (>5mg/day of prednisone or
equivalent doses of other corticosteroids) or other immunosuppressive
agents within 7 days before enrollment.
7. Radiation therapy within 14 days before enrollment.
8. Systemic cytotoxic drugs, including low-dose maintenance chemotherapy
(cyclophosphamide, ifosfamide, bendamustine, methotrexate, or
mercaptopurine, vincristine, etc.), within 14 days before enrollment. If
bridging therapy is given after apheresis, there should be more than a
7-day gap between bridging therapy and CAR-T cell infusion.
9. Anti-PD1 or anti-PDL1 within 4 weeks prior to enrollment.
10. Live vaccines within 4 weeks prior to enrollment.
11. Donor lymphocyte infusion (DLI) within 4 weeks prior to enrollment.
12. Immune stimulation or immunosuppressive therapy (like interferon-α,
interferon-β, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, or
mycophenolate mofetil) within 4 weeks prior to enrollment.
13. Use of clofarabine or cladribine within 3 months prior to enrollment, or
use of PEG-asparaginase within 3 weeks prior to enrollment.
9. Active graft-versus-host disease (GVHD) rated ≥2 on the CIBMTR acute GVHD
grading system or requires systemic steroids at doses greater than
physiological levels.
10. A history of autoimmune diseases in the past 2 years (like Crohn's disease,
rheumatoid arthritis, or systemic lupus erythematosus) that has caused damage
to end organs or requires systemic immunosuppression/systemic disease-modifying
agents.
11. A history of myocardial infarction, cardiac angioplasty or stenting, unstable
angina, or other clinically significant heart diseases within the 12 months
prior to enrollment.
12. A history of genetic syndromes associated with bone marrow failure, such as
Fanconi anemia, Kostmann syndrome, or Schwachman-Diamond syndrome.
13. A history of symptomatic deep vein thrombosis or pulmonary embolism requiring
systemic anticoagulation in the 6 months before enrollment. Subjects need to be
on preventive anticoagulant medication.
14. A history of other malignancies (except for non-melanoma skin cancer, in situ
breast/cervical cancer, and other malignant tumors that have been effectively
controlled without treatment in the past five years).
15. Use of other investigational medicinal products within 30 days prior to
screening.
16. Pregnant or breastfeeding women of childbearing age. Women who have undergone
surgical sterilization or are postmenopausal for at least 2 years are not
considered of childbearing potential.
17. Male and female subjects unwilling to practice contraception from the time they
agree to treatment until 12 months after completing the lymphodepleting
chemotherapy or CAR-T infusion (whichever is longer).
18. Any medical activities that could interfere with the safety or efficacy
evaluation of the study treatment.
19. In the judgment of the investigator, subjects are unlikely to complete all
required study visits or procedures (including follow-ups) or to comply with
the study participation requirements.
Gender:
All
Minimum age:
14 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Anhui Medical University
Address:
City:
Hefei
Zip:
230022
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Ge, MD
Phone:
+86-0551-62923653
Email:
gejian52@163.com
Contact backup:
Last name:
Jian Ge, MD
Start date:
August 24, 2023
Completion date:
September 1, 2026
Lead sponsor:
Agency:
Shanghai First Song Biotechnology Co., LTD
Agency class:
Industry
Source:
Shanghai First Song Biotechnology Co., LTD
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06532643
