Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas

NCT02030834 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 13413, 818607
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Phase IIa study to estimate the efficacy of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as CART-19 or CTL019 cells) in non-Hodgkins Lymphoma (NHL) patients. The duration of active protocol intervention is approximately 24 months from screening visit. The protocol will require approximately 48 months to complete.

Conditions

Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With an Overall Response (i.e. Either Complete Response or Partial Response) Evaluated at Three Months Post Infusion.

  Responders will include those patients achieving complete response (CR), complete response unconfirmed (CRu) and partial response (PR) using anatomic imaging such as CT or MRI to assess tumor volume or, in the event of bone marrow involvement, morphologic and immunohistochemical confirmation that the bone marrow infiltrate has been cleared.

  3 months

Study Arms (3)

Cohort A

EXPERIMENTAL

murine CART19

Biological: CART-19

Cohort B

EXPERIMENTAL

T cell/histiocyte-rich Diffuse Large B Cell Lymphoma (DLBCL) treated with murine CART19

Biological: CART-19

Cohort C

EXPERIMENTAL

Diffuse Large B Cell Lymphoma (DLBCL) treated with humanized CART19

Biological: CART-19

Interventions

CART-19 BIOLOGICAL

Single infusion of CART-19 cells administered by i.v. injection (total dose of 1 - 5 x108 CART-19 cells, calculated as a range of 2-50% transduced cells in total cells).

Cohort A; Cohort B; Cohort C

Eligibility Criteria

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

You may qualify if:

• Male or female subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic SCT) who have a limited prognosis (several months to \<2 year survival) with currently available therapies will be enrolled. The study will enroll 51 evaluable subjects as follows:
• CD19+ Lymphoma
• Cohort A Subjects:
• a. Follicular lymphoma, previously identified as CD19+ i. At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) ii. Patients who progress within 2 years after second or higher line of therapy will be eligible. For instance, patients who have progression of lymphoma \< 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible. Patients may have progression, stable disease or responding disease at the time of enrollment.
• iii. Patients with a history of large cell transformation are eligible. b. Mantle cell lymphoma, previously identified as CD19+ i. Beyond 1st CR with relapsed disease, progressive disease during first line rituximab-chemotherapy combination, or persistent disease after first line rituximab-chemotherapy combination and not eligible or appropriate for conventional allogeneic or autologous SCT.
• ii. Relapsed after prior autologous SCT. c. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
• Cohort B Subjects:
• a. Diffuse large B cell lymphoma, previously identified as CD19+ CD19 i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
• v. Patients with T cell/histiocyte-rich disease as confirmed by surgical pathology report
• Cohort C Subjects:
• a. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.
• Age ≥18 years
• Creatinine \< 1.6 mg/dL
• ALT/AST \< 3x upper limit of normal
• Bilirubin \<2.0 mg/dL, unless subject has Gilbert's Syndrome (\<3.0 mg/dL)

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 pregnancy test at enrollment. A urine pregnancy test will be 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.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).
• HIV infection.
• 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
• Patients in complete remission with no assessable disease.
• 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 (2)

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

• Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. doi: 10.1056/NEJMoa1708566. Epub 2017 Dec 10.

  PMID: 29226764 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

CTL019 chimeric antigen receptor

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Study Officials

• Stephen Schuster, 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: January 7, 2014
• First Posted: January 9, 2014
• Study Start: February 5, 2014
• Primary Completion: September 16, 2019
• Study Completion: September 1, 2020
• Last Updated: June 22, 2023
• Results First Posted: October 5, 2020

Record last verified: 2020-10

Locations

US (1)