Retreatment With CTL019/CTL119

Lymphoma, B-Cell Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04419909
• Other study ID #: UPCC 40419
• Secondary ID: 834286
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2024
• Est. completion date: July 2027

Study information

• Verified date: September 2023
• Source: University of Pennsylvania
• Contact: Stephen J Schuster, MD
• Phone: 215.614.1846
• Email: schustes[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

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.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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