Clinical trial NCT04419909: Retreatment With CTL019/CTL119
Official title: Retreatment With CTL019/CTL119 in Patients With Late Relapse of B-Cell Lymphomas
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Lymphoma, B-Cell
Keywords: CTL019
CTL119
CAR T-cell
CART
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: At time of consent through 1 year after the subject received CTL019/CTL119
Secondary outcomes:
measure: Overall response rate using Cheson 2007 criteria
timeFrame: Month 3 post-infusion
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Stephen J Schuster
role: PRINCIPAL_INVESTIGATOR
References: