NCT04464200

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
2mo left

Started Jul 2020

Longer than P75 for phase_1

Geographic Reach
1 country

7 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress98%
Jul 2020Jul 2026

First Submitted

Initial submission to the registry

July 6, 2020

Completed
Same day until next milestone

Study Start

First participant enrolled

July 6, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 9, 2020

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2026

Last Updated

August 24, 2025

Status Verified

August 1, 2025

Enrollment Period

6 years

First QC Date

July 6, 2020

Last Update Submit

August 22, 2025

Conditions

Diffuse Large B Cell LymphomaPrimary Mediastinal Large B Cell LymphomaTransformed Follicular Lymphoma to Diffuse Large B Cell LymphomaChronic Lymphocytic LeukemiaIndolent Non-Hodgkin LymphomaMarginal Zone LymphomaWaldenstrom MacroglobulinemiaBurkitt's LymphomaPrimary CNS Lymphoma

Keywords

19(T2)28z1XX CAR T cells20-167

Outcome Measures

Primary Outcomes (1)

  • Recommended Phase II Dose (RP2D)

    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.

    28 days post infusion

Secondary Outcomes (1)

  • overall response rate (ORR)

    2 years

Study Arms (1)

19(T2)28z1xx CAR T cells

EXPERIMENTAL

Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10\^6, 50 x 10\^6, 100 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.

Drug: 19(T2)28z1xx CAR T cells

Interventions

19(T2)28z1xx CAR T cellsDRUG

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.

19(T2)28z1xx CAR T cells

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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 12 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Publications (2)

  • Park JH, Palomba ML, Perica K, Devlin SM, Shah G, Dahi PB, Lin RJ, Salles G, Scordo M, Nath K, Valtis YK, Lynch A, Cathcart E, Zhang H, Schoder H, Leithner D, Liotta K, Yu A, Stocker K, Li J, Dey A, Sellner L, Singh R, Sundaresan V, Tong X, Zhao F, Mansilla-Soto J, He C, Meyerson J, Hosszu K, McAvoy D, Wang X, Riviere I, Sadelain M. Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma. J Clin Oncol. 2025 Jul 20;43(21):2418-2428. doi: 10.1200/JCO-24-02424. Epub 2025 Jan 30.

    PMID: 39883889DERIVED

  • 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(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PMID: 34515338DERIVED

Related Links

MeSH Terms

Conditions

Lymphoma, Large B-Cell, DiffuseLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell, Marginal ZoneWaldenstrom MacroglobulinemiaBurkitt Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus Infections

Study Officials

  • Jae Park, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: 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 4 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 and up to 12 patients with B-cell non-Hodgkin lymphoma (same eligibility criteria as the dose-escalation phase).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2020

First Posted

July 9, 2020

Study Start

July 6, 2020

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Last Updated

August 24, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

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 clinicaltrials.gov 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: crdatashare@mskcc.org.

Locations

US(7)