Study of ET190L1 ARTEMIS™ T Cells in Relapsed and Refractory CD19+ Non-Hodgkin's Lymphoma

NCT03379493 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ETUS16CD19AR107
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, single arm, open-label, single institution, phase I study to determine the maximum tolerated dose (MTD) of ET190L1 ARTEMIS™ T cells in patients ≥ 18 years of age with relapsed or refractory CD19+ Non-Hodgkin's lymphoma.

Conditions

Lymphomas Non-Hodgkin's B-Cell

Keywords

relapsed/refractory CD19+ Lymphomas Non-Hodgkin's B-Cell

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Estimate the maximum tolerated dose of ET190L1 ARTEMIS™ T cells in patients with a relapsed and/or refractory CD19+ Non-Hodgkin's lymphoma

  24 months

• Toxicity profile of ET190L1 ARTEMIS™ T-cell treatment

  The frequency of occurrence and severity of treatment-related adverse events, including adverse events of special interest (AESI) will be reported. AESI include: CRS (severity grade 1-5), Tumor Lysis Syndrome, Neutropenic Fever, Cytopenia lasting \>28 days, neurotoxicity (severity grade 1-5), hypogammaglobulinemia and reductions in cardiac function.

  24 months

Secondary Outcomes (5)

• Overall response rate (ORR)

  24 months

• Overall response rate (ORR) in histologic subtypes of CD19+ Non-Hodgkin's lymphoma

  24 months

• Duration of overall response (DOR)

  24 months

• Progression free survival (PFS)

  24 months

• Overall survival (OS)

  24 months

Study Arms (1)

ET190L1 ARTEMIS™ T cells

EXPERIMENTAL

ET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion

Biological: ET190L1 ARTEMIS™ T cells

Interventions

ET190L1 ARTEMIS™ T cells BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) ARTEMIS™ expression construct, administered by intravenous (IV) infusion

ET190L1 ARTEMIS™ T cells

Eligibility Criteria

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

You may qualify if:

• Patients with relapsed/refractory CD19+ Non-Hodgkin's lymphoma of the following subtypes:
• Diffuse large B-cell lymphoma (DLBCL)
• Mantle cell lymphoma (MCL)
• Follicular lymphoma (FL)
• Chronic lymphocytic leukemia and Small lymphocytic lymphoma (CLL/SLL)
• Burkitt's Lymphoma
• Ability to provide written informed consent for the protocol.
• Willingness and ability to comply with scheduled visit, treatment plans, laboratory tests, and other procedures.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group performance status of ≤ 2.
• Evidence of at least one measurable lesion (nodes/nodal masses \> 1.5 cm, extranodal masses \>1.0 cm or PET avid lesions consistent with lymphoma) on imaging with the following exceptions:
• Patients treated with interim chemotherapy for disease control between enrollment and ET190L1 ARTEMIS™ T cell infusion who do not have measurable disease at re-screening are still eligible.
• CLL/SLL with documented B-cell absolute lymphocytosis \> 5 x 109 cells/L peripheral blood or infiltration of lymph nodes and/or bone marrow infiltration by CLL phenotype cells defined as: clonal B cells with majority population co-expressing CD5 and CD19, with surface immunoglobulin (sIg, kappa or lambda but not both) and CD20 (dim), CD23+ (if CD20 or sIg are bright or if CD23 is dim or negative \[atypical CLL phenotype\] then FISH for 11:14 translocation must be performed to differentiate from mantle cell lymphoma).
• Lesions previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• Must have biopsy-proven primary refractory disease or relapsed disease after front-line chemo-immunotherapy (with anti-CD20 mAb in combination with anthracycline-based chemotherapy) or at least one of the following:

You may not qualify if:

• Prior Treatment:
• With any prior anti-CD19/anti-CD19 CAR-T or cellular therapy (prior Blinotumomab therapy is allowed)
• Treatment with any prior gene therapy
• Prior allogeneic hematopoietic stem cell transplant
• Received chemotherapy, radiation or surgical resection of malignancy within 2 weeks prior to the start of conditioning chemotherapy (day -10 to -5).
• Active, uncontrolled serious infection or medical or psychiatric illness, that in the investigator's opinion is likely to interfere with participation in this clinical trial
• Active CNS involvement by malignancy.
• History of seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
• Active replication of hepatitis B or active hepatitis C (HCV RNA positive). Those with prior disease who are PCR negative at enrollment and meet liver function eligibility criterion are eligible.
• Known HIV positive patients
• Patients with unstable angina and/or myocardial infarction within 6 months prior to screening.
• Cardiac arrhythmia not controlled with medical management, evidence of pericardial effusion on imaging that is compromising function.
• Previous or concurrent malignancy with exception of adequately treated basal cell or squamous cell carcinoma, in-situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to study drug infusion, or prostate cancer that was treated with prostatectomy or radiotherapy over 2 years before day 1 of protocol therapy and patients whose PSA is undetectable at study entry.
• Autoimmune disease or history of primary immunodeficiency (excluding Hashimoto's thyroiditis, vitiligo, or DM type I)
• Women who are pregnant or breast feeding.

Sponsors & Collaborators

• Eureka Therapeutics Inc.: lead
• Duke University: collaborator
• Duke Clinical Research Institute: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David A Rizzieri, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 20, 2017
• Study Start: April 4, 2018
• Primary Completion: December 23, 2018
• Study Completion: January 30, 2019
• Last Updated: February 4, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)