Retreatment With CTL019/CTL119

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04419909
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 60
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell	Drug: CD19 redirected autologous T cells (CTL019 or CTL119 cells)	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Retreatment With CTL019/CTL119 in Patients With Late Relapse of B-Cell Lymphomas
• Anticipated Study Start Date: Jul 1, 2022
• Anticipated Primary Completion Date: Jul 1, 2027
• Anticipated Study Completion Date: Jul 1, 2027

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [At time of consent through 1 year after the subject received CTL019/CTL119]

   Safety of retreatment with CTL019/CTL119 as measured by treatment-related events

Secondary Outcome Measures

1. Overall response rate using Cheson 2007 criteria [Month 3 post-infusion]

   Efficacy of retreatment with CTL019/CTL119 as measured by ORR by Cheson 2007 definitions at 3 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Stephen J Schuster, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04419909
• Other Study ID Numbers: UPCC 40419; 834286
• First Posted: Jun 9, 2020
• Last Update Posted: Mar 21, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Pennsylvania: CTL019; CTL119; CAR T-cell; CART
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell

Study Results

No Results Posted as of Mar 21, 2022