Study of LUCAR-20S in Patients With R/R NHL

Sponsor
The First Affiliated Hospital with Nanjing Medical University (Other)
Overall Status
Terminated
CT.gov ID
NCT04176913
Collaborator
Nanjing Legend Biotechnology Co.,Ltd.; The First Affiliated Hospital of USTC west district; Beijing Boren Hospital (Other)
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Study Details

Study Description

Brief Summary

An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma.

Condition or Disease Intervention/Treatment Phase
  • Drug: LUCAR-20S CAR-T cells
Phase 1

Detailed Description

This study is an open, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of donor-derived CD20-directed CAR-T cells administered with lymphodepletion, and to obtain the preliminary efficacy results in subjects who have been diagnosed with relapsed or refractory CD20 positive diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma or small lymphocytic lymphoma. The allo-CAR-T cells will be infused in single-dose.

Study Design

Study Type:
Interventional
Actual Enrollment :
7 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of LUCAR-20S in Patients With Relapsed/Refractory Diffuse Large B-Cell, Follicular, Mantle Cell or Small Lymphocytic Lymphoma
Actual Study Start Date :
Dec 1, 2020
Actual Primary Completion Date :
Dec 9, 2021
Actual Study Completion Date :
Dec 9, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Anti-CD20 Allogeneic CAR-T Cell Therapy

An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma.

Drug: LUCAR-20S CAR-T cells
An Anti-CD20 Allogeneic CAR-T Cell Therapy in Patients with Relapsed/Refractory Diffuse Large B-Cell, Follicular, Mantle Cell or Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicity (DLT) [30 days post infusion]

    DLT assessed by NCI-CTCAE 5.0

  2. Adverse events [90 days post infusion]

    Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0

  3. Concentration of Pharmacokinetics in blood [through study completion, 2 years after infusion of the last subject]

    PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood

  4. Concentration of Pharmacokinetics in bone marrow [through study completion, 2 years after infusion of the last subject]

    PK CAR positive T cells in bone marrow, PK CAR transgene levels in bone marrow

Secondary Outcome Measures

  1. Recommended Phase II dose (RP2D) [30 days post infusion]

    RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion

  2. Overall response rate (ORR) after administration [3 months post infusion]

    Antitumor efficacy by 2014 Lugano criteria

  3. Time to Response (TTR) after administration [3 months post infusion]

    Antitumor efficacy by 2014 Lugano criteria

  4. Duration of remission (DOR) after administration [through study completion, 2 years after infusion of the last subject]

    Antitumor efficacy by 2014 Lugano criteria

  5. Progress Free Survival (PFS) after administration [through study completion, 2 years after infusion of the last subject]

    Antitumor efficacy by 2014 Lugano criteria

  6. Overall Survival (OS) after administration [through study completion, 2 years after infusion of the last subject]

    Antitumor efficacy by 2014 Lugano criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Signed informed consent form (ICF)

  2. Age 18 Years to 75 Years

  3. Pathological diagnosis of refractory/relapsed CD20+ non-Hodgkin's lymphoma (one of the following):

  4. Diffuse large B-cell lymphoma (DLBCL)

  5. Follicular lymphoma (FL)

  6. Mantle cell lymphoma (MCL)

  7. Small lymphocytic lymphoma (SLL)

  8. Measurable disease as defined by 2014 Lugano criteria at Screening

  9. Refractory/relapsed disease after standard-of- care treatment as following (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). Subject must have documented evidence of progressive disease on or within 12 months of their last regimen.

  10. DLBCL: Refractory/relapsed after at least 1 prior line of therapy, must have been treated with anti-CD20 monoclonal antibody

  11. FL: Refractory/relapsed after at least 2 prior lines of therapy, must have been treated with anti-CD20 monoclonal antibody

  12. MCL: Refractory/relapsed after at least 2 prior lines of therapy

  13. SLL: Refractory/relapsed after at least 2 prior lines of therapy

  14. Laboratory criteria at Screening

① Blood routine: NE≥1.0×109/L;HGB≥8g/dL;PLT≥50×109/L

② Blood biochemical parameters:

  1. Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)

  2. Aspartate and alanine aminotransferases (AST, ALT) ≤ 3 times ULN (in the presence of liver metastasis, ULN 5 times)

  3. Estimated glomerular filtration rate (eGFR) > 60mL/min

  4. Life expectancy > 12 weeks

  5. Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

Exclusion Criteria:
  1. Any malignancy besides the NHL categories under study, exceptions include

  2. Any other malignancy curatively treated and disease-free for at least 2 years prior to enrollment

  3. History of non-melanoma skin cancer with sufficient treatment and currently no evidence of recurrence

  4. Prior treatment with an allogeneic stem cell transplant

  5. Prior treatment with genetic therapy

  6. Prior treatment with chimeric antigen receptor T (cells) CAR-T therapy directed at CD20 target

  7. 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)

  8. Prior antitumor therapy with insufficient washout period

  9. Targeted therapy, epigenetic therapy, experimental drug therapy or experimental invasive treatment with medical apparatus and instruments 14 days or five half-lives, whichever is shorter before lymphodepletion

  10. Use of monoclonal antibodies 21 days prior to lymphodepletion

  11. Chemotherapy within 14 days prior to lymphodepletion

  12. Radiotherapy within 14 days prior to lymphodepletion

  13. Participated in other clinical trials within 30 days prior to lymphodepletion

  14. With central nervous system involvement

  15. Women in pregnancy or lactation

  16. Being fertile and unable to use effective conception during treatment and 100 days after CAR-T infusion

  17. Active autoimmune disease or history of autoimmune disease within 3 years

  18. With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism

  19. The following cardiac conditions

  20. New York Heart Association (NYHA) stage III or IV congestive heart failure

  21. Left ventricular ejection fraction (LVEF) less than (<)45%

  22. Uncontrolled cardiac arrhythmia post-medication

  23. With a history of myocardial infraction or unstable angina pectoris within the past 6 months

  24. Constrictive pericarditis

  25. Cardiomyopathy

  26. Pulse oximetry of <96% on room air

  27. Active or uncontrolled infection requiring parenteral antibiotics, or any evidence of severe active viral/bacterial infection or uncontrolled systemic fungal infection

  28. Uncontrolled diabetes mellitus, defined as fast serum glucose > 1.5 times ULN

  29. Concurrent use of corticosteroids or other immunosuppressant medications for chronic disease

  30. Concurrent use of hematopoietic growth factor

  31. Stroke or seizure within 6 months of signing ICF

  32. Have received any live, attenuated vaccine within 4 weeks prior to lymphodepletion

  33. Have underwent major surgical operation within 2 weeks prior to lymphodepletion, or anticipate to undergo a major surgical operation during the study process or within 2 weeks posterior to study treatment(with the exception of anticipated local anesthesia surgery)

  34. Known life threatening allergies, hypersensitivity, or intolerance to LUCAR-20S CAR-T cells or its excipients, including dimethyl sulfoxide (DMSO)

  35. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol

Contacts and Locations

Locations

Site City State Country Postal Code
1 Oncology Department,The First Affiliated Hospital of USTC west district Hefei Anhui China 230000
2 Hematological Department, People's Hospital of Jiangsu Province Nanjing Jiangsu China 210029
3 Hematological Department,Beijing Boren Hospital Beijing China 100070

Sponsors and Collaborators

  • The First Affiliated Hospital with Nanjing Medical University
  • Nanjing Legend Biotechnology Co.,Ltd.; The First Affiliated Hospital of USTC west district; Beijing Boren Hospital

Investigators

  • Principal Investigator: Wei Xu, PhD& MD, The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
  • Principal Investigator: Kaiyang Ding, PhD& MD, Anhui Provincial Cancer Hospital
  • Principal Investigator: Kai Hu, PhD& MD, Beijing Boren Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
WEI XU, Chief Physician of hematology department, The First Affiliated Hospital with Nanjing Medical University
ClinicalTrials.gov Identifier:
NCT04994587
Other Study ID Numbers:
  • BM2L201904
  • BM2L201904
  • NCT04994587
First Posted:
Nov 25, 2019
Last Update Posted:
Jan 10, 2022
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 10, 2022