Brief Title
LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma
Official Title
An Open Label, Single Center, Single Arm Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma
Brief Summary
An open label, single center, single arm Phase I study to evaluate the safety, tolerability,
and pharmacokinetics of LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T-cell lymphoma.
Detailed Description
This study is an open, dose escalation/dose regimen finding study to assess the safety and
pharmacokinetics of CD4-directed CAR-T cells administered with lymphodepletion, and to obtain
the preliminary efficacy results in subjects who have been diagnosed with relapsed or
refractory CD4 positive peripheral T-cell lymphoma, not otherwise specified,
angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma. The auto-CAR-T cells
will be infused in single-dose.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Dose limiting toxicity (DLT)
Secondary Outcome
Overall response rate (ORR) after administration
Condition
CD4+ T-cell Lymphoma
Intervention
Efficacy of LCAR-T2C CAR-T cells
Study Arms / Comparison Groups
LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T-cell lym
Description: An open label, single center, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T-cell lymphoma.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
34
Start Date
December 30, 2019
Completion Date
February 28, 2023
Primary Completion Date
November 29, 2022
Eligibility Criteria
Inclusion Criteria:
1. Signed informed consent form (ICF)
2. Age 18 Years to 75 Years
3. Pathological diagnosis of refractory/relapsed CD4+ T-cell lymphoma (one of the
following):
1. Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL, NOS)
2. Angioimmunoblastic T-Cell Lymphoma (AITL)
3. Anaplastic Large Cell Lymphoma (ALCL)
4. Measurable disease as defined by 2014 Lugano criteria at Screening
5. Refractory/relapsed disease after at least 1 prior line of therapy (Undergone at least
2 complete cycle of therapy for each line, unless PD been documented as the best
response to the regimen) and not eligible or appropriate for HSCT (Auto/ Allo).
Subjects must have documented disease progression (PD) during the most recent
treatment or within 12 months after treatment. In addition, subjects who are
refractory or non-responsive to their most recent line of treatment are eligible.
(Non-responsive disease is defined as either failure to achieve partial response (PR)
and abrove or development of progressive disease (PD) while on therapy).
6. Life expectancy ≥ 12 weeks
7. Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 -2.
8. The screening phase clinical laboratory values meet the following criteria. Laboratory
test(s) may be repeated once, to determine if the subject qualifies for study
participation :
- Blood routine: HGB≥8g/dL；PLT≥50×10^9/L; ANC≥1.0×10^9/L; LY≥0.3×10^9/L ② Blood
biochemical parameters:
1. Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 times ULN (in the
presence of liver metastasis, AST and ALT≤5 times ULN)
2. Serum creatinine (Scr) ≤ 1.5 times ULN, estimated glomerular filtration rate
(eGFR) > 60mL/min (only when Scr>1.5 times ULN)
3. Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
4. Total cholesterol <300 mg / dL or <7.75 mmol / L
5. Triglyceride < 2.5 times ULN
6. International Normalized Ratio (INR) ≤ 1.5 times ULN, PT≤ 1.5 times ULN,
APTT≤ 1.5 times ULN
Exclusion Criteria:
1. Prior treatment with CAR-T therapy directed at any target.
2. Any therapy that is targeted to CD4.
3. Prior treatment with an allogeneic stem cell transplant
4. Any malignancy besides the T-cell lymphoma categories under study, exceptions include
1. Any other malignancy curatively treated and disease-free for at least 2 years
prior to enrollment
2. History of non-melanoma skin cancer with sufficient treatment and currently no
evidence of recurrence
5. Those who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis
B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C
virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab)
6. The following cardiac conditions:
1. New York Heart Association (NYHA) stage III or IV congestive heart failure
2. Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to
enrollment
3. History of clinically significant ventricular arrhythmia or unexplained syncope,
not believed to be vasovagal in nature or due to dehydration
4. History of severe non-ischemic cardiomyopathy
5. Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or
multiple-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
7. Prior antitumor therapy as follows, prior to apheresis:
1. Targeted therapy, epigenetic therapy, or treatment with an investigational drug
or used an invasive investigational medical device within 14 days or at least 5
half-lives, whichever is less.
2. Monoclonal antibody treatment for multiple myeloma within 21 days.
3. Cytotoxic therapy within 14 days.
4. Radiotherapy within 14 days.
8. Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade
1 or less except for alopecia or peripheral neuropathy.
9. With central nervous system involvement.
10. Participated in other clinical trials within 30 days.
11. Serious underlying medical condition, such as:
1. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal
infection
2. Active autoimmune disease or a history of autoimmune disease within 3 years
3. Overt clinical evidence of dementia or altered mental status
12. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this
study or within 100 days after receiving study treatment.
13. Plans to father a child while enrolled in this study or within 100 days after
receiving study treatment.
14. With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation
disorders and hypersplenism
15. Pulse oximetry of <96% on room air
16. Received a cumulative dose of corticosteroids equivalent to ≥70 mg of prednisone
within 7 days prior to apheresis
17. Concurrent use of hematopoietic growth factor
18. Concurrent anti-cancer therapy including radiotherapy
19. Stroke or seizure within 6 months of signing ICF
20. Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis
21. Major surgery within 2 weeks prior to apheresis, or has surgery planned during the
study or within 2 weeks after study treatment administration. (Note: subjects with
planned surgical procedures to be conducted under local anesthesia may participate.)
22. Known life threatening allergies, hypersensitivity, or intolerance to LCAR-T2C CAR-T
cells or its excipients, including DMSO (refer to Investigator's Brochure)
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Wei Xu, PhD& MD, +8668306034, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04219319
Organization ID
2019-SR-370.A4
Responsible Party
Principal Investigator
Study Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
Nanjing Legend Biotechnology Co.,Ltd.
Study Sponsor
Wei Xu, PhD& MD, Principal Investigator, The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
Verification Date
January 2021