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

NCT03085173 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 16-1570
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia (CLL); Relapsed; Refractory

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  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.

  occurring within 30 days from the last infusion

Study Arms (1)

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

EXPERIMENTAL

Following 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.

Biological: EGFRt/19-28z/4-1BBL CAR T cells

Interventions

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

Cohorts of 3-6 patients will be infused with escalating doses of EGFRt/19-28z/4-1BBL CAR T cells to establish the maximum tolerated dose (MTD). There are 4 planned dose levels: 1 x 10\^5, 3 x 10\^5, 1 x 10\^6, and 3 x 10\^6 CAR T cells/kg.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Juno Therapeutics, Inc., a Bristol-Myers Squibb Company: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Chronic Lymphocytic Leukemia (CLL)

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 21, 2017
• Study Start: March 15, 2017
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-04

Locations

US (1)