Clinical Trials /

19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers

NCT04464200

Description:

The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of 19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find this dose, they can test it in future participants to see if it is effective in treating their relapsed/refractory B-cell cell cancers. This study will also look at whether 19(T2)28z1xx CAR T cells work against participants' cancer.

Related Conditions:
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Indolent Non-Hodgkin Lymphoma
  • Marginal Zone Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Richter Syndrome
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers
  • Official Title: A Phase I Study of CD19-Targeted 19(T2)28z1xx Chimeric Antigen Receptor (CAR) Modified T Cells in Adult Patients With Relapsed or Refractory B-cell Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 20-167
  • NCT ID: NCT04464200

Conditions

  • Diffuse Large B Cell Lymphoma
  • Primary Mediastinal Large B Cell Lymphoma
  • Transformed Follicular Lymphoma to Diffuse Large B Cell Lymphoma
  • Chronic Lymphocytic Leukemia
  • Indolent Non-Hodgkin Lymphoma
  • Marginal Zone Lymphoma
  • Waldenstrom Macroglobulinemia
  • Burkitt's Lymphoma
  • Primary CNS Lymphoma

Interventions

DrugSynonymsArms
19(T2)28z1xx CAR T cells19(T2)28z1xx CAR T cells

Purpose

The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of 19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find this dose, they can test it in future participants to see if it is effective in treating their relapsed/refractory B-cell cell cancers. This study will also look at whether 19(T2)28z1xx CAR T cells work against participants' cancer.

Trial Arms

NameTypeDescriptionInterventions
19(T2)28z1xx CAR T cellsExperimentalCohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 5 planned flat-dose levels: 25x10^6, 50 x 10^6, 100 x 10^6, 150 x 10^6, and 200 x 10^6 CAR T cells and one de-escalation dose: 12.5 x 10^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1.
  • 19(T2)28z1xx CAR T cells

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Dose Escalation Phase:

          -  Histologically confirmed DLBCL and large B cell lymphoma, including

               -  DLBCL, not otherwise specified (NOS), or

               -  Transformed DLBCL from follicular lymphoma, or

               -  High-grade B cell lymphoma (excluding Burkitt's lymphoma), or

               -  Primary mediastinal large B cell lymphoma AND

               -  Chemotherapy refractory disease, defined as a failure to achieve at least a
                  partial response or disease progression within 6 months to the last therapy, OR

               -  Disease progression or recurrence in ≤12 months of prior autologous stem cell
                  transplant (ASCT), OR

               -  Relapsed disease after 2 or more prior chemoimmunotherapies with at least one
                  containing an anthracycline and CD20 directed therapy

          -  Patients need to have radiographically documented disease

        Dose Expansion phase:

        Cohort 1: same disease subtypes as in the Dose Escalation Phase

        Cohort 2 (exploratory cohort) will include the following additional disease histology:

          -  Patients with CLL

               -  Refractory to or relapsed after at least 1 prior chemo or chemoimmunotherapies
                  (e.g., FCR, BR) and 1 prior biologic agent (e.g. BTK, PI3K inhibitors,
                  venetoclax) requiring further treatment, OR

               -  Refractory to or relapsed after at least 2 prior biologic agents (e.g. Ibrutinib,
                  idelalisib, venetoclax, except a single agent anti-CD20 monoclonal antibody)
                  requiring further treatment

          -  Patients with iNHL (FL, MZL, WM):

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

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

          -  Patients with Burkitt's lymphoma or transformed CLL to large cell lymphoma (i.e.
             Richter's transformation):

               -  Refractory to or relapsed after at least 1 prior multiagent systemic chemo or
                  chemoimmunotherapy

        Exclusion Criteria:

          -  ECOG performance status ≥2.

          -  Patients with active CNS disease

          -  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 the 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

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

          -  Patients with prior allogeneic hematopoietic stem cell transplant are eligible, if
             more than 3 months from transplant and if patients have no active graft versus host
             disease (GvHD) and not on systemic immunosuppressive therapy.

          -  Prior CD19-directed therapy including CD19 CAR T cells is allowed, as long as
             expression of CD19 is confirmed by flow cytometry or immunohistochemistry.

          -  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 the skin.

          -  Patients with 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:Recommended Phase II Dose (RP2D)
Time Frame:28 days post infusion
Safety Issue:
Description:Dose escalation will use a 3+3 design. DLT-evaluable participants are defined as those participants who were infused with 19(T2)28z1XX CAR T cells and who were monitored for toxicities during the first 28 days of post infusion.

Secondary Outcome Measures

Measure:overall response rate (ORR)
Time Frame:2 years
Safety Issue:
Description:Response and progression of the disease will be evaluated in this study using the Lugano Classification

Details

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

Trial Keywords

  • 19(T2)28z1XX CAR T cells
  • 20-167

Last Updated

July 6, 2020