T-cells or EBV Specific CTLs, Advanced B-Cell NHL and CLL

NCT00709033 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 22899-ATECRABATECRAB
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

Patients on this study have a type of lymph gland cancer called non-Hodgkin Lymphoma or chronic Lymphocytic Leukemia. Their lymphoma or CLL has come back or has not gone away after treatment. Because there is no standard treatment for the cancer at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and CLL. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now attached to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T cells seem to be able to kill tumors, but they don't last very long and so their chances of fighting the cancer are limited. Investigators found that T cells work better if they also attach a protein called CD28 to the T cells. This protein makes the T cells more active and survive longer. Also they found that T cells that are also trained to recognize the virus that causes infectious mononucleosis (called Epstein Barr Virus or EBV) can stay in the blood stream for many years. These CD19-CD28 chimeric receptor T cells and CD19 chimeric-EBV specific T cells are investigational products not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe to administer, to see how long each of the T cell populations (CD19-CD28 and CD19-EBV-specific) last, to assess what the side effects are, and to evaluate whether this therapy might help people with lymphoma or CLL.

Conditions

Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Keywords

refractory; relapsed; low; intermediate-grade; Non-Hodgkin lymphoma; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity

  Dose-limiting toxicity is defined as development of NCI grade III - IV non-hematologic or grade IV hematologic toxicity that can be attributed to the study treatment

  6 weeks

Secondary Outcomes (2)

• Survival and function of CD19CAR PBTLs and EBV-CTLs

  15 years

• Number of patients with tumor response

  6 weeks

Study Arms (1)

autologous or syngeneic PBTLs and EBV-CTLs

EXPERIMENTAL

The subject will be assigned a dose of CD19-CD28 chimeric receptor T cells at study entry.

Biological: autologous or syngeneic PBTLs and EBV-CTLs

Interventions

autologous or syngeneic PBTLs and EBV-CTLs BIOLOGICAL

Three dose levels are being evaluated namely: GROUP 1 PBTL CD19CAR-28 zeta 2x10exp7 cells/m2 and EBV-CTL CD19CAR zeta 2x10exp7 cells/m2 GROUP 2 PBTL CD19CAR-28 zeta 1x10exp8cells/m2 and EBV-CTL CD19CAR zeta 1x10exp8 cells/m2 GROUP 3 PBTL CD19CAR-28 zeta 2x10exp8 cells/m2 and EBV-CTL CD19CAR zeta 2x10exp8 cells/m2

autologous or syngeneic PBTLs and EBV-CTLs

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• FOR TREATMENT:
• Recurrent low or intermediate grade B-cell lymphoma or B-CLL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory intermediate B cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation.
• CD19-positive tumor
• EBV seropositivity (in patient and donor, as applicable)
• Recovered from the acute toxic effects of all prior chemotherapy at least a week before entering this study.
• Not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six weeks.
• No treatment with rituximab within the previous 8 weeks.
• ANC \> 500, Hgb \> 8.0\*
• Bilirubin less than 3 times the upper limit of normal\*
• AST less than 5 times the upper limit of normal\*
• Serum creatinine less than 3 times upper limit of normal\*
• Pulse oximetry of \> 90% on room air\*
• Adequate pulmonary function with FEV1, FVC and DLCO \>35%\* of expected corrected for hemoglobin
• Karnofsky or Lansky score of \> 60%.
• Available autologous or syngeneic transduced EBV-specific cytotoxic T lymphocytes and peripheral blood T-cells with 15% or greater expression of CD19CAR determined by flow-cytometry.

You may not qualify if:

• History of hypersensitivity reactions to murine protein-containing products.
• Pregnant or lactating.
• Tumor in a location where enlargement could cause airway obstruction.
• Active infection with HIV, HBV, HCV or CMV.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, Liu H, Creighton CJ, Gee AP, Heslop HE, Rooney CM, Savoldo B, Dotti G. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014 Jun 12;123(24):3750-9. doi: 10.1182/blood-2014-01-552174. Epub 2014 Apr 29.

  PMID: 24782509 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

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

Study Officials

• Carlos Ramos, MD

  Baylor College of Medicine

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: July 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2025
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (2)