Clinical Trials /

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

NCT03379493

Description:

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.

Related Conditions:
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ETUS16CD19AR107
  • NCT ID: NCT03379493

Conditions

  • Lymphomas Non-Hodgkin's B-Cell

Interventions

DrugSynonymsArms
ET190L1-ARTEMIS™ T cellsET190L1-ARTEMIS™ T cells

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
ET190L1-ARTEMIS™ T cellsExperimentalET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion

    Eligibility Criteria

            Inclusion Criteria:
    
              -  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:
    
                   1. 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.
    
                   2. 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).
    
                   3. 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:
    
                        1. with no unfavorable cytogenetics and have failed ≥ 3 prior line(s) of
                           therapy.
    
                        2. 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:
    
                   1. Renal function:
    
                      1. Creatinine clearance ≥45ml/min
    
                   2. Liver function:
    
                        1. 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.
    
                        2. 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
    
                   3. Pulmonary function:
    
                      1. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea
                      and pulse oximetry of ≥ 88% on room air.
    
                   4. 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
    
                   5. Bone marrow reserve without transfusion defined as:
    
                        1. Absolute neutrophil count (ANC) ≥ 1,000/mm3
    
                        2. Absolute lymphocyte count (ALC) ≥ 300/mm3, and absolute number of CD3+ T
                           cells > 150/mm3
    
                        3. Platelets ≥ 50,000/mm3
    
                        4. 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).
    
                   1. Medically acceptable contraceptives for females include:
    
                        1. Surgical sterilization (such as a tubal ligation or hysterectomy).
    
                        2. Approved hormonal contraceptives (such as birth control pills, patches,
                           implants, or injections).
    
                        3. Barrier methods (such as condoms or diaphragms) used with a spermicide.
    
                        4. An intrauterine device (IUD).
    
                   2. 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.
    
                   3. Medically acceptable contraceptives for males include:
    
                        1. Surgical sterilization (such as a vasectomy)
    
                        2. A condom used with a spermicide
    
                   4. 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.
    
            Exclusion Criteria:
    
              -  Prior Treatment:
    
                   1. With any prior anti-CD19/anti-CD19 CAR-T or cellular therapy (prior Blinotumomab
                      therapy is allowed)
    
                   2. Treatment with any prior gene therapy
    
                   3. Prior allogeneic hematopoietic stem cell transplant
    
                   4. 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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Maximum Tolerated Dose
    Time Frame:24 months
    Safety Issue:
    Description:Estimate the maximum tolerated dose of ET190L1-ARTEMIS™ T cells in patients with a relapsed and/or refractory CD19+ Non-Hodgkin's lymphoma

    Secondary Outcome Measures

    Measure:Overall response rate (ORR)
    Time Frame:24 months
    Safety Issue:
    Description: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
    Measure:Overall response rate (ORR) in histologic subtypes of CD19+ Non-Hodgkin's lymphoma
    Time Frame:24 months
    Safety Issue:
    Description:Evaluate the efficacy of ET190L1-ARTEMIS™ T cells in histologic subtypes of CD19+ Non-Hodgkin's lymphoma.
    Measure:Duration of overall response (DOR)
    Time Frame:24 months
    Safety Issue:
    Description:Evaluate duration of overall response (DOR)
    Measure:Progression free survival (PFS)
    Time Frame:24 months
    Safety Issue:
    Description:Evaluate progression free survival (PFS)
    Measure:Overall survival (OS)
    Time Frame:24 months
    Safety Issue:
    Description:Evaluate overall survival (OS)

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Eureka Therapeutics Inc.

    Trial Keywords

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

    Last Updated

    April 5, 2018