Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

NCT05842707 | Recruiting Phase 1 DMC

• 1 other identifier: 2023-008
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

To find the highest tolerable dose of dualCAR-NK19/70 (a type of cell therapy) that can be given to patients who have B-cell lymphoma that is relapsed or refractory.

Conditions

Refractory or Relapsed B-cell Non-Hodgkin Lymphoma

Keywords

B-cell Non-Hodgkin Lymphoma; CAR NK Cells Targeting CD19/CD70; Cord Blood-derived

Outcome Measures

Primary Outcomes (1)

• incidence of dose limiting toxicity(DLTs)

  To evaluate the safety,tolerabitility,and determine the recommended dosage of cord blood-derived CAR NK cells targeting CD19/CD70

  up to 28 days

Secondary Outcomes (5)

• Objective Response Rate（ORR）

  6 months

• Complete Remission Rate(CRR)

  3 months

• Overall survival(OS)

  Up to 3 years

• Duration of Response(DOR)

  Up to 3 years

• progression-free survival(PFS)

  Up to 3 years

Other Outcomes (2)

• Incidence of Adverse Events

  through study completion; an average of 1 year,up to 3 years

• Exploratory Objectives

  Up to 3 years

Study Arms (1)

Part 1 (dose escalation) and Part 2 (dose expansion)

EXPERIMENTAL

Part 1 (dose escalation) the dose of dualCAR-NK19/70 participants receive will depend on when you join this study. Up to 3 dose levels of dualCAR-NK19/70 will be tested. About 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of dualCAR-NK19/70. Each new group will receive a higher dose of dualCAR-NK19/70 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of dualCAR-NK19/70 is found. Part 2 (dose expansion) Participants will receive dualCAR-NK19/70 at the recommended dose that was found in Part 1.

Drug: dualCAR-NK19/70 cell

Interventions

dualCAR-NK19/70 cell DRUG

Given by IV (vein)

Also known as: CAR-NK cell

Part 1 (dose escalation) and Part 2 (dose expansion)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the study and sign the informed consent;
• Age 18-75, male and female;
• Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other Indolent B-cell NHL transforming types:
• （A） Relapsed or Refractory DLBCL and tFL after 2 lines Immunotherapy or chemotherapy ; （B） Definition of Refractory large B cell lymphoma (SCHOLAR - 1 Research Standard) : disease progression after more than 4 courses of standard Immunotherapy or chemotherapy; Or the time of disease stabilization ≤ 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation (auto-HSCT); （C） Relapsed or Refractory MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; （D） Relapsed or Refractory disease after chemotherapy including rituximab and anthracycline.
• There was at least one measurable lesion with the longest diameter ≥ 1.5cm;
• Estimated life expectancy of more than 12 weeks other than primary disease;
• Previously confirmed diagnosis as CD19+ or CD70+ B-NHL.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3.
• Adequate reserve of organ function:
• （A） Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) ≤2.5 times the Upper Limit of Normal (ULN) for age; （B） A creatinine clearance (as estimated either by a direct urine collection or Cockcroft-Gault Equation) \> 60mL/min; （C） Total bilirubin and alkaline phosphatase ≤1.5 times the Upper Limit of Normal (ULN) for age; （D） glomerular filtration rate \> 50 ml/min （E） Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA); （F） Baseline oxygen saturation \>92% on room air （G） Absolute neutrophil count \> 1000/μL, Platelet count \> 45,000/μL ,Hemoglobin \> 80g/L;
• Once previous autologous hematopoietic stem cell transplantation (auto-HSCT) is allowed;
• For systemic therapy(Such as systemic chemotherapy, systemic radiotherapy and immunotherapy), at least 3 weeks，for Targeted drug therapy alone，at least 2 weeks，must have elapsed at the time of cell infusion;
• Either having failed or Relapsed after CAR-T therapy at 3 months of assessment;
• Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study. Women of childbearing potential must have a negative serum or urine pregnancy test.
• The viral load of severe coronavirus disease 2019 (COVID-19) is undetectable per quantitative PCR and/or nucleic acid testing for two tests.

You may not qualify if:

• Allergic to any of the components of cell products;
• Previous or concurrent of other type of maligant tumors;
• Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous autologous hematopoietic stem cell transplantation (auto-HSCT); Or receiving of anti-GVHD therapy;
• Known history of systemic gene therapy within the prior 3 months;
• Active systemic fungal, viral, or bacterial infection (except for simple urinary tract infections and bacterial pharyngitis), however, Preventive treatment is permitted;
• Known history of infection with hepatitis B (HBsAg positive, but HBV-DNA\<1000 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV infection;
• Class III or IV heart failure as defined by the New York Heart Association;
• Persisting toxicities (\>grade 1, except for clinically non-significant toxicities such as alopecia, fatigue, and anorexia) due to prior trerapy;
• Known history of active seizures or presence of seizure activities or other central nervous system disease;
• Have evidence of central nervous system lymphoma(CNS lymphoma) on CT or MRI;
• Breast-feeding woman;
• Any circumstances that possibly increase the risk of subjects or interfere with study results, which judged by investigator.

Sponsors & Collaborators

• Aibin Liang，MD，Ph.D.: lead

Study Sites (1)

Shanghai Tongji Hospital, Tongji University School of Medicine

Shanghai, Shanghai Municipality, 200065, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• aibin Liang

  Shanghai Tongji Hospital, Tongji University School of Medicine

  STUDY CHAIR

Central Study Contacts

aibin Liang

CONTACT

18601670600; lab7182@tongji.edu.cn

Ping Li

CONTACT

13564181131; lilyforever76@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Hematology and Oncology Center, Shanghai Tongji Hospital

Study Record Dates

• First Submitted: March 25, 2023
• First Posted: May 6, 2023
• Study Start: January 18, 2023
• Primary Completion (Estimated): January 18, 2028
• Study Completion (Estimated): January 18, 2029
• Last Updated: May 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)