Memory Enriched T Cells Following Stem Cell Transplant in Treating Patients With Recurrent B-Cell Non-Hodgkin Lymphoma

NCT02051257 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 13277NCI-2014-00133P50CA107399
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the highest possible dose of memory enriched T cells that can be given following standard stem cell transplant before unmanageable side effects are seen in patients with B-cell non-Hodgkin lymphoma that has returned after previous treatment. A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Memory enriched T cells will be made from a patient's own T cells that are genetically modified in a laboratory. This means that the T cells are changed by inserting additional pieces of deoxyribonucleic acid (genetic material) into the cell to make it recognize and kill lymphoma cells. Memory enriched T cells may kill the cells that are not killed by stem cell transplant and may lower the chances of the cancer recurring.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Incidence of dose limiting toxicities (DLTs), defined as any grade 3 or higher toxicity, any grade 3 or greater autoimmune toxicity, or failure for a research participant with documented T cell persistence to engraft by day 21 post HSCT

  Toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) and the Cytokine Release Syndrome (CRS) Clinical Symptoms \& Revised Grading System. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

  Up to 28 days

• Incidence of adverse events attributable to the cellular immunotherapy product

  Toxicity and adverse events will be assessed using CTCAE v4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

  Up to 15 years

• MTD of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells based on DLTs

  Toxicity and adverse events will be assessed using CTCAE v4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

  28 days

• MTD of autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells based on DLTs

  Toxicity and adverse events will be assessed using CTCAE v 4.0 and the revised CRS grading system. Tables will be created to summarize all toxicities and side effects by arm (cell type), dose, course, organ, severity and attribution. Rates and associated 95% confidence limits will be estimated.

  28 days

Secondary Outcomes (2)

• Engraftment of the transferred T cell product

  Up to 28 days

• Levels of CD19+ B-cell precursors in the bone marrow, used as a surrogate for the in vivo effector function of transferred CD19-specific T-cells

  Up to 36 months

Study Arms (2)

Arm 1 (autologous TCM-enriched T cells)

EXPERIMENTAL

Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TCM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT.

Biological: Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells; Other: Laboratory Biomarker Analysis

Arm 2 (autologous TN/MEM-enriched T cells)

EXPERIMENTAL

Patients receive autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing TN/MEM-enriched T cells IV over 10 minutes on day 2 or 3 following HSCT.

Biological: Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes; Other: Laboratory Biomarker Analysis

Interventions

Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells BIOLOGICAL

Given IV

Also known as: CD19R:CD28:lentiviral/EGFRt+ T cells

Arm 1 (autologous TCM-enriched T cells)

Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes BIOLOGICAL

Given IV

Also known as: CD19R(EQ)28zetaEGFRt+ Tn/mem Cells, CD19R(EQ)28zetaEGFRt+ Tn/Tmem

Arm 2 (autologous TN/MEM-enriched T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm 1 (autologous TCM-enriched T cells); Arm 2 (autologous TN/MEM-enriched T cells)

Eligibility Criteria

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

You may qualify if:

• Research participants enrolled are patients with an indication to be considered for HSCT, who are diagnosed with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) (e.g. diffuse large B-cell lymphoma \[DLBCL\], mantle cell lymphoma \[MCL\], or transformed NHL), and that have either (1) recurrence/progression following prior therapy, or (2) verification of high-risk disease in first or subsequent remission
• Karnofsky performance status (KPS) of \>= 70% at time of enrollment
• Life expectancy \>= 16 weeks at time of enrollment
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of intermediate or high grade B-cell NHL (e.g., DLBCL, MCL, or transformed NHL)
• Negative serum pregnancy test for women of child-bearing potential
• Research participant has an indication to be considered for autologous stem cell transplantation
• All subjects must have the ability to understand and the willingness to sign a written informed consent
• ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS:
• Research participant has a released cryopreserved T cell product
• Research participant did not have evidence of disease progression after salvage therapy and therefore underwent an autologous myeloablative transplantation with hematopoietic progenitor cell autologous (HPC\[A\]) rescue procedure
• Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
• Not requiring pressor support, not having symptomatic cardiac arrhythmias
• Lack of acute renal failure/requirement for dialysis, as evidenced by creatinine \< 1.6 mg/dL
• Total bilirubin =\< 5.0 mg/dL

You may not qualify if:

• Research participants with any uncontrolled illness including ongoing or active infections; research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) positive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
• Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
• Research participants with a history of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab
• Research participants with known brain metastases (central nervous system \[CNS\] involvement either parenchymal or leptomeningeal involvement)
• Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
• Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
• History of allogeneic HSCT or prior autologous HSCT
• Any standard contraindications to myeloablative HSCT per standard of care practices at COH
• Dependence on corticosteroids
• Defined as doses of corticosteroids of greater than or equal to 5 mg/day of prednisone or equivalent doses of other corticosteroids
• Note: topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed
• Currently receiving another investigational agent
• Active autoimmune disease requiring systemic immunosuppressive therapy
• Research participants will be excluded, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Elizabeth Budde, MD, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2014
• First Posted: January 31, 2014
• Study Start: June 19, 2014
• Primary Completion (Estimated): March 2, 2027
• Study Completion (Estimated): March 2, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (1)