A Study of EXP039 Treatment in Subjects With r/r NHL Subjects

• ClinicalTrials.gov Identifier: NCT04693676
• Recruitment Status: Unknown
• First Posted: January 5, 2021
• Last Update Posted: April 13, 2021
• Sponsor: First Affiliated Hospital of Zhejiang University
• Information provided by (Responsible Party): First Affiliated Hospital of Zhejiang University

Tracking Information

• First Submitted Date: December 3, 2020
• First Posted Date: January 5, 2021
• Last Update Posted Date: April 13, 2021
• Actual Study Start Date: July 10, 2020
• Estimated Primary Completion Date: July 10, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 31, 2020)

• MTD [ Time Frame: up to12 Months ]
  maximum tolerated dose or clinical recommended dose
• DLT [ Time Frame: up to 28 days after EXP039 infusion ]
  Dose limiting toxicity
• AE/SAE/AESI [ Time Frame: up to12 Months ]
  adverse events (AE), serious adverse event (SAE), pay particular attention to adverse events (AESI) (including cytokine release syndrome (CRS), and nerve toxicity), laboratory tests (type, frequency and severity), vital signs and ECG abnormality rate.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 31, 2020)

• EXP039 CAR expansion and persistence [ Time Frame: up to12 Months ]
  After EXP039 infusion, peripheral blood EXP039 CAR expansion and persistence in vivo.
• Objective response rate (ORR) [ Time Frame: Time Frame 4weeks,12 weeks, 6 months, 9 months, 12 months ]
  Complete response (CR) rate plus partial response (PR) rate by Lugano 2014 criteria
• Duration of response (DOR) [ Time Frame: Time Frame: up to 12 months ]
  The time from the date of first response (PR or better) until the date of disease progression after EXP039 infusion
• Progression-free survival (PFS) [ Time Frame: Time Frame: 4weeks, 12 weeks, 6 months, 9 months ,12 months ]
  The time from EXP039 infusion to the date of progression as assessed by Lugano 2014 criteria or death
• Overall survival rate (OSR) [ Time Frame: Time Frame: 12 weeks, 6 months, 12 months ]
  The time from EXP039 infusion to the date of death

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of EXP039 Treatment in Subjects With r/r NHL Subjects
• Official Title: A Phase 1 Study Evaluating Safety and Efficacy of EXP039 Treatment in Subjects With Relapsed and/or Refractory NHL

Brief Summary

This is a single-arm, open label, dose escalation, phase I study of EXP039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma.

Condition of disease:B cell Non-Hodgkin's Lymphoma Intervention/treatment: Biological/Vaccine: CD19/CD20-direct CAR-T cells. phase: phase 1

Detailed Description

This is a single-arm, open label, "3+3" dose escalation, phase I study to evaluate the safety and preliminary efficacy of EXP039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma. 10 patients are planned to be enrolled.

Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of EXP039. Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to EXP039 infusion. All subjects who have received EXP039 infusion will be followed for up to 12 months.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Hodgkin's B-cell Lymphoma

Intervention

Biological: CD19/CD20-directed CAR-T cells

Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously

Other Name: EXP039

Study Arms

Experimental: EXP039

Autologous EXP039 administered by intravenous (IV) infusion

Intervention: Biological: CD19/CD20-directed CAR-T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 31, 2020): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 10, 2022
• Estimated Primary Completion Date: July 10, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The patient volunteered to participate in the study and signed the Informed Consent;
2. Age between 18 and 70 (including 18 and 70), male or female;
3. Expected survival ≥ 12 weeks;
4. ECOG score 0-2
5. CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria;
6. Patients with a clear diagnosis of relapsed and/or refractory B-NHL, including DLBCL, FL and MCL;
7. For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause of intolerance should be recorded;
8. No contraindications of apheresis;
9. At least one measurable lesion according to Lugano 2014 criteria;
10. Adequate organ function.

Exclusion Criteria:

1. Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
2. Active HIV, HBV, HCV or treponema pallidum infection ;
3. Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy;
4. Any uncontrolled, active disease that prevents participation in the trial;
5. Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion;
6. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
7. Patients who have been previously infected with tuberculosis;
8. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of EXP039;
9. Patients with central nervous system involvement;
10. Any systemic antitumor therapy was performed within 2 weeks before conditional treatment chemotherapy pretreatment;
11. Prior use of any CAR-T cell product or other genetically modified T-cell therapy;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04693676
• Other Study ID Numbers: 0702-025
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: First Affiliated Hospital of Zhejiang University
• Original Responsible Party: Same as current
• Current Study Sponsor: First Affiliated Hospital of Zhejiang University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jie Jin, PhD&MD; First Affiliated Hospital of Zhejiang University College of Medicine

• PRS Account: First Affiliated Hospital of Zhejiang University
• Verification Date: November 2020