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A Trial of "Armored" CAR T Cells Targeting CD19 For Patients With Relapsed CD19+ Hematologic Malignancies

NCT03085173

Description:

The purpose of this phase I study is to test the safety of different dose levels of specially prepared cells collected from the patient called "modified T cells". The investigators want to find a safe dose of modified T cells for patients with this type of cancer that has progressed after standard therapy. The investigators also want to find out what effects these modified T cells have on the patient and the cancer. For patients who were treated, had progression of disease and were removed from study, duplicate enrollment is permitted if it is determined the patients could receive a benefit. If the patients meet all eligibility criteria, they can be enrolled onto study a second time as a new accrual, and receive treatment in a higher dose level cohort.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial of "Armored" CAR T Cells Targeting CD19 For Patients With Relapsed CD19+ Hematologic Malignancies
  • Official Title: A Phase I Trial of CD19-Targeted EGFRt/19-28z/4-1BBL "Armored" Chimeric Antigen Receptor (CAR) Modified T Cells in Patients With Relapsed or Refractory CD19+ Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 16-1570
  • NCT ID: NCT03085173

Conditions

  • Chronic Lymphocytic Leukemia (CLL)
  • Relapsed
  • Refractory

Interventions

DrugSynonymsArms
EGFRt/19-28z/4-1BBL CAR T cellsEGFRt/19-28z/4-1BBL CAR T cells

Purpose

The purpose of this phase I study is to test the safety of different dose levels of specially prepared cells collected from the patient called "modified T cells". The investigators want to find a safe dose of modified T cells for patients with this type of cancer that has progressed after standard therapy. The investigators also want to find out what effects these modified T cells have on the patient and the cancer. For patients who were treated, had progression of disease and were removed from study, duplicate enrollment is permitted if it is determined the patients could receive a benefit. If the patients meet all eligibility criteria, they can be enrolled onto study a second time as a new accrual, and receive treatment in a higher dose level cohort.

Trial Arms

NameTypeDescriptionInterventions
EGFRt/19-28z/4-1BBL CAR T cellsExperimentalFollowing enrollment, patients will undergo leukapheresis of peripheral blood for further T cell enrichment, activation and genetic modification using a retroviral vector encoding a CD19targeted CAR, the co-stimulatory ligand 4-1BBL and the EGFRt safety system (EGFRt/19-28z/4-1BBL). These T cells will be expanded and after the appropriate number of cells is generated, the modified T cells may be infused fresh or frozen for later use according to standard operation procedures. Modified T cell infusions will be administered 2-7 days following completion of the treating investigator's choice of conditioning chemotherapy. Serial sampling of blood and bone marrow will be performed following treatment to assess toxicity, therapeutic effects, and survival of the genetically modified T cells.
  • EGFRt/19-28z/4-1BBL CAR T cells

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have CD19+ B cell malignancy with relapsed or refractory disease,
             defined as below:

        Patients with CLL:

          -  Refractory to or relapsed after at least 2 prior chemo or chemoimmunotherapy (e.g.
             FCR, BR) requiring further treatment

          -  Refactory to or relapsed after at least 1 prior biologic agent (e.g. Ibrutinib,
             idelalisib, venetoclax, except a single agent anti-CD20 monoclonal antibody) requiring
             further treatment

        Patients with iNHL (FZ, MZL, WM):

          -  Refractory or relapsed after at least 2 lines of chemoimmunotherapy (including at
             least one course of anti-CD20 antibody)

          -  Refractory or relapsed after at least 1 prior biologic agent (e.g. lenalidomide,
             ibrutinib, idelalisib)

          -  Patients must have measurable disease (for WM patients, measureable disease is
             demonstrable monoclonal paraprotein and bone marrow involvement)

        Patients with DLBCL, Transformed B cell lymphoma, or High grade B cell lymphoma:

          -  Refractory to or relapsed after 1 or more prior chemoimmunotherapies with at least one
             containing an anthracycline and CD20 directed therapy

          -  Transplant ineligible

          -  Biopsy proven relapsed disease

        Patients with ALL, CML in lymphoid blast crisis or Burkitt's lymphoma:

          -  Refractory to at least 1 prior induction chemotherapy

          -  Relapsed after at least 1 prior multiagent systemic chemotherapy that included
             induction and consolidation

          -  Patients with Philadelphia chromosome-positive ALL must have failed a second
             generation tyrosine kinase inhibitor

               -  Age ≥ 18 years of age

               -  Creatinine ≤2.0 mg/100 ml, direct bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x
                  upper limit of normal (ULN)

               -  Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by
                  pulse oximetry

        Exclusion Criteria:

          -  Karnofsky performance status <70

          -  Pregnant or lactating women. Women and men of childbearing age should use effective
             contraception while on this study and continue for 1 year after all treatment is
             finished

          -  Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan

          -  Patients with active known autoimmune disease are ineligible

          -  Patients with following cardiac conditions will be excluded:

               -  New York Heart Association (NYHA) stage III or IV congestive heart failure

               -  Myocardial infarction </= 6 months prior to enrollment

               -  History of clinically significant ventricular arrhythmia or unexplained syncope,
                  not believed to be vasovagal in nature or due to dehydration <6 months prior to
                  enrollment

               -  History of severe non-ischemic cardiomyopathy with EF </=20%

          -  Patients with HIV or active hepatitis B or hepatitis C infection are ineligible

          -  Patients with uncontrolled systemic fungal, bacterial, viral or other infection are
             ineligible

          -  Patients with any concurrent active malignancies as defined by malignancies requiring
             any therapy other than expectant observation or hormonal therapy, with the exception
             of squamous and basal cell carcinoma of skin

          -  Patients with history or presence of clinically significant neurological disorders
             such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible

          -  Any other issue which, in the opinion of the treating physician, would make the
             patient ineligible for the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:occurring within 30 days from the last infusion
Safety Issue:
Description:Cohorts of 3-6 patients each will be treated with escalating doses of modified T cell. At least 3 patients will be treated at each dose level with an accrual of no more than 2 patients per month within each dose level. At least two weeks will elapse from the first patient's T cell infusions before the second patient is treated (on dose level 1) to allow for toxicity and safely assessment. All patients treated at the preceding dose level will be observed a minimum of 4 weeks before dose escalation occurs.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • CAR T Cells Targeting CD19
  • EGFRt/19-28z/4-1BBL
  • 16-1570

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