Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma
Phase I Study of Cellular Immunotherapy Using Central Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Peripheral Blood Stem Cell Transplantation for Patients With High-Risk Intermediate Grade B-Lineage Non-Hodgkin Lymphoma
3 other identifiers
interventional
30
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating patients with recurrent or high-risk non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2013
Longer than P75 for phase_1
1 active site
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
First Submitted
Initial submission to the registry
March 19, 2013
CompletedFirst Posted
Study publicly available on registry
March 21, 2013
CompletedStudy Start
First participant enrolled
October 8, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 9, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
CompletedOctober 6, 2025
October 1, 2024
4.3 years
March 19, 2013
October 2, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Adverse events attributed to Tcm adoptive transfer as reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.
Up to 15 years
MTD of CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells based on dose limiting toxicities
Graded according to the NCI CTCAE version 4.0.
Up to day 28
Secondary Outcomes (2)
Engraftment of the transferred T cell products
Up to 21 days
CD19+ B cell precursors in the peripheral blood as a surrogate for the in vivo effector function of transferred CD19-specific T cells
Up to 28 days
Study Arms (1)
Treatment (genetically modified T cell infusion)
EXPERIMENTALPatients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor per current standard operating policies. Patients undergo myeloablative conditioning regimen per institutional standards beginning day -7 followed by hematopoietic stem cell transplantation on day 0. Patients receive CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2 or 3 (may be delayed up to day 45 if the patient is not yet eligible). Patients who experience disease progression and have not experienced DLTs at greater than or equal to 100 days post HSCT will be allowed to receive an optional second T cell infusion.
Interventions
Given IV
Undergo autologous hematopoietic stem cell transplantation
Correlative studies
Eligibility Criteria
You may qualify if:
- Research participants enrolled are patients with an indication to be considered for HSCT, who are diagnosed with intermediate grade B-cell NHL (e.g., DLBCL, MCL or transformed NHL), and that have either recurrence/progression following prior therapy, or verification of high-risk disease in first remission
- Karnofsky performance status of \>= 70% and a 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 the history of intermediate grade B-cell NHL (e.g., DLBCL, MCL or transformed NHL)
- Negative serum pregnancy test for women of childbearing potential
- Research participant has an indication to be considered for autologous stem cell transplantation
- All patients must have the ability to understand and the willingness to sign a written informed consent
- ELIGIBILITY TO UNDERGO AUTOLOGOUS MYELOABLATIVE TRANSPLANTATION WITH HEMATOPOETIC PROGENITOR CELL (HPC)A RESCUE
- Research participant meets all standard clinical parameters for candidates of autologous transplant as described in the current COH Hematopoietic Cell Transplant Standard Operating Policies, Procedures and Protocols
- Patient Evaluation \& Selection or Deferral for hematopoietic cell transplantation (HCT)
- Research participant is scheduled to receive a standard chemotherapy-based conditioning regimen, such as cyclophosphamide, carmustine, etoposide (CBV) or carmustine, etoposide, cytarabine, melphalan (BEAM)
- Research participant has a cryopreserved unselected HPCA product of at least 3 x 10\^6/kg CD34+ cells
- Research participant does not have evidence of disease progression after salvage therapy
- ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS
- Research participant has a released cryopreserved T cell product
- +6 more criteria
You may not qualify if:
- Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment; research participants with any signs of 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab
- Research participants with known brain metastases (central nervous system \[CNS\] involvement or parenchymal or leptomeningeal involvement)
- Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
Related Publications (2)
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: 34515338DERIVEDWang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS, Mott MR, Norris AP, Wong CW, Urak RZ, Chang WC, Khaled SK, Siddiqi T, Budde LE, Xu J, Chang B, Gidwaney N, Thomas SH, Cooper LJ, Riddell SR, Brown CE, Jensen MC, Forman SJ. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016 Jun 16;127(24):2980-90. doi: 10.1182/blood-2015-12-686725. Epub 2016 Apr 26.
PMID: 27118452DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elizabeth Budde
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 19, 2013
First Posted
March 21, 2013
Study Start
October 8, 2013
Primary Completion
January 9, 2018
Study Completion
June 1, 2026
Last Updated
October 6, 2025
Record last verified: 2024-10