Trials / Completed

CompletedNCT01029366

CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy

Pilot Study of Redirected Autologous T-cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patient With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 26 (actual)

Sponsor: University of Pennsylvania · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This is a Pilot/Phase I, single arm, single center, open label study to determine the safety, efficacy and cellular kinetics of CART19 (CTL019) in chemotherapy resistant or refractory CD19+ leukemia and lymphoma subjects. The study consists of three Phases: 1\) a Screening Phase, followed by 2) an Intervention/Treatment Phase consisting of apheresis, lymphodepleting chemotherapy (determined by the Investigator and based on subject's disease burden and histology, as well as on the prior chemotherapy history received), infusions of CTL019, tumor collection by bone marrow aspiration or lymph node biopsy (optional, depending on availability), and 3) a Follow-up Phase. The suitability of subjects' T cells for CTL019 manufacturing was determined at study entry. Subjects with adequate T cells were leukapheresed to obtain large numbers of peripheral blood mononuclear cells for CTL019 manufacturing. The T cells were purified from the peripheral blood mononuclear cells, transduced with TCR-ζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration. The number of subjects who had inadequate T cell collections, expansion or manufacturing compared to the number of subjects who had T cells successfully manufactured is a primary measure of feasibility of this study. Unless contraindicated and medically not advisable based on previous chemotherapy, subjects were given conditioning chemotherapy prior to CTL019 infusion. The chemotherapy was completed 1 to 4 days before the planned infusion of the first dose of CTL019. Up to 20 evaluable subjects with CD19+ leukemia or lymphoma were planned to be dosed with CTL019. A single dose of CTL019 (consisting of approximately 5x10\^9 total cells, with a minimal acceptable dose for infusion of 1.5x10\^7 CTL019 cells) was to be given to subjects as fractions (10%, 30% and 60% of the total dose) on Day 0, 1 and 2. A second 100% dose of CTL019 was initially permitted to be given on Day 11 to 14 to subjects, providing they had adequate tolerance to the first dose and sufficient CTL019 was manufactured.

Detailed description

Primary objectives: 1\. To evaluate the safety and feasibility of a single target dose of 5 times 10e9 total cells, acceptable range of 1.5 times 10e7 to 5 times 10e9 total cells comprised of autologous CART-19 cells that express the TCR zeta and 4-1 BB costimulatory domain. Secondary objectives: 1. Proof of mechanism: determine if 2nd generation CAR expressing 4-1BB costimulation domains have improved persistence in patients. 2. Proof of concept: determine the effects of CART-19 on CD19 expression in vivo. 3. Proof of bioactivity: Evaluate changes in systemic soluble immune factors in patients 4. Proof of bioactivity: Evaluate impact of CART19 treatment on tumor burden 5. Explore whether CART-19 cells retain anti-tumor activity in vivo. 6. Determine if host immunity develops against CART-19. 7. Characterize the relative subsets of CART-19 T cells (Tcm, Tem, and Treg). 8. Describe survival and response rates

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	CART-19	Autologous T cells purified from the peripheral blood mononuclear cells of subjects, transduced with TCR-ζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration.

Timeline

Start date: 2010-03-17
Primary completion: 2015-07-01
Completion: 2016-05-01
First posted: 2009-12-10
Last updated: 2023-06-22
Results posted: 2017-02-28

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT01029366. Inclusion in this directory is not an endorsement.