Dose Optimization Trial of CD19 Redirected Autologous T Cells

NCT01747486 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 03712, 816556
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, parallel group study to determine the optimal dose of CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR Zeta and 4-1 BB co-stimulatory domains) of the two dose levels being assessed (1-5x10e8 vs. 1-5x10e7 CART-19 cells). This trial will be conducted in two stages.

Conditions

Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL

Outcome Measures

Primary Outcomes (1)

• Number of Patients Achieving Complete Response Within 3 Months

  Complete response (including complete response with incomplete marrow recovery) within 3 months (in evaluable patients). The eveluable set comprise of patients who have received CART19 at intended dose level and completed at least 3-month follow-up after the infusion or discontinued due to disease progression, new cancer therapy or death.

  3 months

Study Arms (2)

Target dose of 1-5x10e8

EXPERIMENTAL

Arm 1: Target dose of 1-5x10e8 CART-19 cells (calculated as range of 10-50% transduced cells in 1 x10e9 total cells)

Biological: CART-19

Target dose of 1-5x10e7

EXPERIMENTAL

Arm 2: Target dose of 1-5x10e7 CART-19 cells (calculated as the range of 10-50% transduced cells in 1 x10e8 total cells)

Biological: CART-19

Interventions

CART-19 BIOLOGICAL

CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR zeta and 4-1BB costimulatory domains)

Target dose of 1-5x10e7; Target dose of 1-5x10e8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented CD19+ CLL or SLL
• Successful test expansion of T-cells
• At least 2 prior chemotherapy regimens, not including single agent monoclonal antibody (rituxan) therapy. Single agent ofatumumab will be counted as a regimen. -Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior regimen.
• Patients who progress within 2 years after the second or higher line of therapy will be eligible. For instance, patients who had progression \< 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible.
• Subject is not appropriate candidate for a potentially curative allogeneic SCT due to the state of disease, co-morbid illness, lack of an available donor, or patient declines Performance status (ECOG) 0 or 1
• Age \>/= 18 years
• Adequate organ system function including:
• Creatinine \< 1.6 mg/dl
• ALT/AST \< 3x upper limit of normal
• Total Bilirubin \<2.0 mg/dl
• Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
• Have no active GVHD and require no immunosuppression
• Are more than 6 months from transplant
• No contraindications for leukapheresis
• Left Ventricular Ejection fraction \>40%

You may not qualify if:

• Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection
• Any uncontrolled active medical disorder that would preclude participation as outlined
• HIV infection
• Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Pregnant or lactating women. Female study participants must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
• Uncontrolled active infection
• Active hepatitis or hepatitis infection
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• HIV infection
• Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment on the retreatment cohort.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Abramsonc Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• van Bruggen JAC, Martens AWJ, Fraietta JA, Hofland T, Tonino SH, Eldering E, Levin MD, Siska PJ, Endstra S, Rathmell JC, June CH, Porter DL, Melenhorst JJ, Kater AP, van der Windt GJW. Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy. Blood. 2019 Jul 4;134(1):44-58. doi: 10.1182/blood.2018885863. Epub 2019 May 10.

  PMID: 31076448 DERIVED

• Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett DM, Lacey SF, Melenhorst JJ, McGettigan SE, Cook DR, Zhang C, Xu J, Do P, Hulitt J, Kudchodkar SB, Cogdill AP, Gill S, Porter DL, Woyach JA, Long M, Johnson AJ, Maddocks K, Muthusamy N, Levine BL, June CH, Byrd JC, Maus MV. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016 Mar 3;127(9):1117-27. doi: 10.1182/blood-2015-11-679134. Epub 2016 Jan 26.

  PMID: 26813675 DERIVED

MeSH Terms

Interventions

CTL019 chimeric antigen receptor

Results Point of Contact

• Title: Noelle Frey, MD
• Organization: Abramson Cancer Center of the University of Pennsylvania

noelle.frey@uphs.upenn.edu

215-662-6901

Study Officials

• Noelle Frey, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: December 11, 2012
• Study Start: January 2, 2013
• Primary Completion: December 13, 2017
• Study Completion: April 6, 2018
• Last Updated: June 22, 2023
• Results First Posted: February 26, 2019

Record last verified: 2019-08

Locations

US (1)