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Lymphomas Non-Hodgkin's B-CellPhase 1NCT03379493

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

A Phase 1 study testing ET190L1 ARTEMIS™ T cells in people with Lymphomas Non-Hodgkin's B-Cell, run by Eureka Therapeutics Inc. at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphomas Non-Hodgkin's B-Cell
What is being tested?
ET190L1 ARTEMIS™ T cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
4 Apr 2018to 30 Jan 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • For subjects with DLBCL: relapsed or refractory disease after ≥ 2 prior line(s) of therapy. For both de novo and transformed disease, patients must have received at least 1 prior regimen with anti-CD20 mAb and anthracycline.
  • For subjects with FL or SLL: relapsed or refractory disease after ≥ 2 prior line(s) of therapy.
  • For subjects with CLL: must be relapsed or refractory disease and:
  • with no unfavorable cytogenetics and have failed ≥ 3 prior line(s) of therapy.
  • with unfavorable cytogenetics including del17p/mutated p53 or unmutated immunoglobulin heavy chain variable region relapsed or refractory disease after ≥ 2 prior line(s) of therapy which must have included ibrutinib.
  • For subjects with MCL: relapsed or refractory disease after at least 1 prior regimen with chemoimmunotherapy.
  • For subjects with Burkitt's: relapsed or refractory disease after at least 1 prior line of therapy.
  • Any patient, with subtypes listed above, having either failed autologous HSCT after at least 1 prior regimen, or those patients ineligible for, but not an appropriate candidate, or not consenting to autologous HSCT.
  • Adequate organ function parameters are set according to what the treating physician defines as adequate organ function and are acceptable for participation in this trial. These criteria are defined as:
  • Renal function:
  • 1. Creatinine clearance ≥45ml/min
  • Liver function:
  • AST/ALT ≤ 3x the institutional ULN, except for people with liver involvement by their lymphoma, who may be included if AST/ALT ≤ 5x the institutional ULN.
  • Total bilirubin ≤ 2x the institutional ULN with the exception of patients with Gilbert syndrome; patients with Gilbert syndrome may be included if their total bilirubin is ≤ 3.0x ULN and direct bilirubin is ≤ 2x ULN
  • Pulmonary function:
  • 1. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oximetry of ≥ 88% on room air.
  • Cardiac function:
  • 1. Must be hemodynamically stable at the time of ET190L1 ARTEMIS™ T cell administration and have LVEF ≥ 45% confirmed by echocardiogram or MUGA scan
  • Bone marrow reserve without transfusion defined as:
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3
  • Absolute lymphocyte count (ALC) ≥ 300/mm3, and absolute number of CD3+ T cells > 150/mm3
  • Platelets ≥ 50,000/mm3
  • Hemoglobin ≥ 8 g/dL
  • Women who are pregnant will be excluded from the study. A woman of child-bearing potential, defined as all women physiologically capable of becoming pregnant, will have a blood pregnancy test and the test must be negative to participate in this study. Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months following infusion of ET190L1 ARTEMIS™ T cells and until ET190L1 ARTEMIS™ T cells are no longer present by PCR (with surveillance to cease at 5 years).
  • Medically acceptable contraceptives for females include:
  • Surgical sterilization (such as a tubal ligation or hysterectomy).
  • Approved hormonal contraceptives (such as birth control pills, patches, implants, or injections).
  • Barrier methods (such as condoms or diaphragms) used with a spermicide.
  • An intrauterine device (IUD).
  • Contraceptive measures such as Plan B, sold for emergency use after unprotected sex, are not acceptable methods for routine use. If the woman does become pregnant during this study or if the woman has unprotected sex, she must inform the study physician immediately.
  • Medically acceptable contraceptives for males include:
  • Surgical sterilization (such as a vasectomy)
  • A condom used with a spermicide
  • Contraceptive measures such as Plan B, sold for emergency use after unprotected sex, are not acceptable methods for routine use. The man should inform his partner of the potential for harm to an unborn child. She should know that if pregnancy occurs, he will need to report it to the study doctor, and she should promptly notify her doctor.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: Open-label Phase I Study of ET190L1 ARTEMIS™ T Cells in Relapsed and Refractory CD19+ Non-Hodgkin's Lymphoma

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.

Read the detailed description

The trial will follow a traditional dose-escalation model to establish the MTD and recommended phase 2 dose (RP2D) of infused ET190L1 ARTEMIS™ T cells following lympho-depleting chemotherapy. Two sequential cohorts of patients will be recruited to fulfill this study, those in the dose escalation cohort (for determination of MTD and RP2D) and those in the expansion cohort (treated on the RP2D). The study will have concurrent phases of screening, pre-treatment, treatment, primary follow-up, safety, and survival follow-up. The total duration of the study involvement for the patient is 15 years. Efficacy will be assessed until progression and safety will be assessed throughout the full duration of the study. Twelve to 24 patients will be treated to determine the MTD. Following determination of the MTD, an expansion cohort consisting of 6 patients per disease subtype (n= 30) will be recruited.

Being tested
ET190L1 ARTEMIS™ T cells
Keywords
relapsed/refractory CD19+ Lymphomas Non-Hodgkin's B-Cell
Medical subject headings
Lymphoma, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ET190L1 ARTEMIS™ T cellsBiological

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

Study groups in NCT03379493
Study groupRoleWhat they receive
ET190L1 ARTEMIS™ T cellsExperimentalET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion
Receives: Biological: ET190L1 ARTEMIS™ T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 24 months

  2. 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.

    Measured: 24 months

Secondary outcomes (5)

  1. Overall response rate (ORR)

    Evaluate the efficacy of ET190L1 ARTEMIS™ T cell therapy, defined as overall response rate (ORR), including CR or PR, of patients with relapsed/refractory CD19+ Non-Hodgkin's lymphoma who receive human ET190L1 ARTEMIS™ T cell therapy. Evaluation, staging and response assessment will be carried out using the Lugano classification

    Measured: 24 months

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

    Evaluate the efficacy of ET190L1 ARTEMIS™ T cells in histologic subtypes of CD19+ Non-Hodgkin's lymphoma.

    Measured: 24 months

  3. Duration of overall response (DOR)

    Evaluate duration of overall response (DOR)

    Measured: 24 months

  4. Progression free survival (PFS)

    Evaluate progression free survival (PFS)

    Measured: 24 months

  5. Overall survival (OS)

    Evaluate overall survival (OS)

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2017
  2. Study start4 Apr 2018
  3. Primary completion23 Dec 2018
  4. Study completion30 Jan 2019

Why it stopped: Sponsor's Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03379493
Sponsor's protocol ID
ETUS16CD19AR107
Status last verified
Jan 2019
First submitted
13 Dec 2017
Last updated
4 Feb 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ET190L1 ARTEMIS™ T cells in people with Lymphomas Non-Hodgkin's B-Cell, run by Eureka Therapeutics Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 49 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor's Decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03379493.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2019.

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