Retreatment With CTL019/CTL119

Retreatment With CTL019/CTL119 in Patients With Late Relapse of B-Cell Lymphomas

This research study is designed to evaluate the effects of retreatment with CTL019/CTL119 in patients with late relapse of B-cell lymphomas.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Drug: CD19 redirected autologous T cells (CTL019 or CTL119 cells)

Detailed Description

This is a single arm open label trial that will assess the safety and efficacy of retreatment with CTL019/CTL119 chimeric antigen receptor (CAR) modified T cells in patients who have late relapse of diffuse large B-cell or follicular lymphoma after achieving complete remission from prior CTL019/CTL119 treatment. Patients eligible for this protocol will have been treated initially with CTL019/CTL119 under UPCC13413/NCT02030834, have experienced a durable complete response (defined as ≥ 6 months duration), and have a residual manufactured CTL019/CTL119 product available. This protocol will serve subjects with no available potentially curative treatment options (such as autologous or allogeneic stem cell transplantation) who have a limited prognosis (months to < 2 year expected survival) with available therapies.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Stephen J Schuster, MD; Phone Number: 215.614.1846; Email: schustes@pennmedicine.upenn.edu
• Study Contact Backup: Name: Emerging Medicine; Phone Number: 855-216-0098; Email: PennCancerTrials@careboxhealth.com

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
      • Contact: Emerging Medicine; Phone Number: 855-216-0098; Email: PennCancerTrials@careboxhealth.com
      • Contact: Stephen J Schuster, MD; Phone Number: 855-216-0098; Email: PennCancerTrials@careboxhealth.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diffuse Large B-Cell Lymphoma or Follicular lymphoma, previously identified as CD19+
2. Previously treated on UPCC13413/ NCT02030834 with CTL019/CTL119, with historical manufactured product available at Penn for reinfusion
3. Previous complete response to CAR T-cells with a duration ≥ 6 months (defined as 168 days)
4. No available curative treatment options (such as autologous or allogeneic HSCT) with limited prognosis (several months to < 2 year survival) with currently available therapies.
5. Age ≥18 years
6. Creatinine < 1.6 mg/dL
7. ALT/AST < 3x upper limit of normal
8. Bilirubin < 2.0 mg/dL, unless subject has Gilbert's Syndrome (≤3.0 mg/dL)
9. Measurable or assessable disease according to the "Revised Response Criteria for Malignant Lymphoma" (Cheson et al., J. Clin. Onc., 2007)88. Patients in complete remission with no evidence of disease are not eligible.
10. Performance status (ECOG) 0 or 1.
11. Left Ventricle Ejection Fraction (LVEF) > 40% confirmed by ECHO/MUGA
12. Agree to contraceptive requirements outlined in Section 4.3.
13. Provide written informed consent.

Exclusion Criteria:

1. Uncontrolled active infection.
2. Active hepatitis B or hepatitis C infection.
3. Any uncontrolled active medical disorder that would preclude participation as outlined.
4. Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).
5. HIV infection.
6. Patients with active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment
7. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Retreatment with CTL019/CTL119; All subjects will receive retreatment with CTL019/CTL119 and be followed per the schedule of procedures.	Drug: CD19 redirected autologous T cells (CTL019 or CTL119 cells); Retreatment with CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19 cells) or huCD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19 cells) in subjects with late relapse of B-cell lymphomas.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Safety of retreatment with CTL019/CTL119 as measured by treatment-related events	At time of consent through 1 year after the subject received CTL019/CTL119

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate using Cheson 2007 criteria	Efficacy of retreatment with CTL019/CTL119 as measured by ORR by Cheson 2007 definitions at 3 months	Month 3 post-infusion

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Stephen J Schuster, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: June 3, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: CTL019; CAR T-cell; CTL119; CART
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tisagenlecleucel
• Other Study ID Numbers: UPCC 40419; 834286 (Other Identifier: University of Pennsylvania Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No