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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04464200
Recruitment Status : Recruiting
First Posted : July 9, 2020
Last Update Posted : April 6, 2021
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE July 6, 2020
First Posted Date  ICMJE July 9, 2020
Last Update Posted Date April 6, 2021
Actual Study Start Date  ICMJE July 6, 2020
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2020)
Recommended Phase II Dose (RP2D) [ Time Frame: 28 days post infusion ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2020)
overall response rate (ORR) [ Time Frame: 2 years ]
Response and progression of the disease will be evaluated in this study using the Lugano Classification
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE 19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a standard phase I open-label dose-escalation trial. Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the MTD. There are 5 planned dose levels with one additional de-escalation dose level. A 3+3 design will be used to establish the RP2D. Once the RP2D is determined, the study will open to Dose Expansion phase with two cohorts. Cohort 1 will comprise of up to 12 patients with B-cell non-Hodgkin lymphoma (same eligibility criteria as the dose-escalation phase). Cohort 2 will include up to 12 patients with other CD19+ B cell hematologic malignancies including CLL, indolent B-cell lymphoma, primary CNS lymphoma, and Richter's transformation.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: 19(T2)28z1xx CAR T cells
2-7 days following the completion of the conditioning chemotherapy, patients will receive the CAR- T cells by IV infusion over 1-3 days depending on the dose level and formulation of the final CAR- T cells.
Study Arms  ICMJE Experimental: 19(T2)28z1xx CAR T cells
Cohorts 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.
Intervention: Drug: 19(T2)28z1xx CAR T cells
Publications * Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9:CD013365. doi: 10.1002/14651858.CD013365.pub2. Review.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2020)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jae Park, MD 646-608-3743
Contact: M. Lia Palomba, MD 646-608-3711
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04464200
Other Study ID Numbers  ICMJE 20-167
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to:
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Takeda
Investigators  ICMJE
Principal Investigator: Jae Park, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP