Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia

NCT02030847 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 21413, 818626
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, single arm, open-label phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR/4-1BB) co-stimulatory domains (referred to as CART-19 cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Inclusion criteria are designed to include adult patients aged greater than 18 with B cell ALL, relapsed or refractory, with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have limited prognosis (greater than 12 weeks survival expectancy) with currently available therapies. The study product is CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 108 transduced CAR T cells.

Conditions

Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options

Outcome Measures

Primary Outcomes (1)

• Overall Complete Remission Rate at Day 28 After CART-19 Therapy

  Overall Complete Remission Rate (ORR) which includes complete remission (CR) and CR with incomplete blood count recovery (CRi) at Day 28. Overall Complete Remission Rate = CR+ CRi

  28 Days

Secondary Outcomes (1)

• Best Overall Response

  from the start of the treatment until death, last follow up, relapse or start of new anticancer therapy, whichever comes first, assessed up to 12 months

Study Arms (1)

Arm1

EXPERIMENTAL

phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-19" cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.

Biological: CART-19

Interventions

CART-19 BIOLOGICAL

CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 10\^8 transduced CAR T cells

Arm1

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form must be obtained prior to any study procedure
• Relapsed or refractory B-cell ALL
• st or greater BM relapse OR
• Any marrow relapse after allogeneic HSCT and \> 100 days from transplant OR
• For patients with refractory disease:
• i. \< 60 years old that have not achieved a CR after \> 2 or more chemotherapy regimens ii. \>60 years old that have not achieved a CR after 1 prior chemotherapy regimen d. Patients with Ph+ ALL are eligible if they have failed tyrosine kinase inhibitor therapy
• Documentation of CD19 tumor expression in bone marrow or peripheral blood by flow cytometry within 3 months of screening.
• Adequate organ function defined as:
• Creatinine \< 1.6 mg/dl
• ALT/AST \< 3x upper limit of normal range
• Direct bilirubin \<2.0 mg/dl
• Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen \> 92% on room air, and DLCO \> 40% (corrected for anemia if clinically appropriate)
• Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
• Bone marrow with ≥ 5% lymphoblasts
• Male or female age ≥ 18 years

You may not qualify if:

• Isolated extramedullary disease relapse
• Active hepatitis B or active hepatitis C
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• HIV infection
• Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
• Active CNS involvement by malignancy. Note: Patients with history of CNS disease that has been effectively treated will be eligible provided that treatment was \>4 weeks before enrollment
• Pregnant or nursing (lactating) women, female study participants of reproductive potential must have a negative serum or urine pregnancy test within 48 hours before infusion
• Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
• Pregnant or lactating women.
• Active hepatitis B or hepatitis C
• 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
• Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Frey NV, Shaw PA, Hexner EO, Pequignot E, Gill S, Luger SM, Mangan JK, Loren AW, Perl AE, Maude SL, Grupp SA, Shah NN, Gilmore J, Lacey SF, Melenhorst JJ, Levine BL, June CH, Porter DL. Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Feb 10;38(5):415-422. doi: 10.1200/JCO.19.01892. Epub 2019 Dec 9.

  PMID: 31815579 DERIVED

MeSH Terms

Conditions

Recurrence

Interventions

CTL019 chimeric antigen receptor

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2014
• First Posted: January 9, 2014
• Study Start: February 27, 2014
• Primary Completion: April 26, 2018
• Study Completion: April 26, 2018
• Last Updated: June 22, 2023
• Results First Posted: May 24, 2019

Record last verified: 2019-08

Locations

US (1)