Administration of T Lymphocytes for Prevention of Relapse of Lymphomas

NCT02663297 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: LCCC 1524-ATLR01HL114564
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration. In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the patient's genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD30. This antibody floats around in the blood and can detect and stick to cancer cells called lymphoma cells because they have a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. The purpose of this research study is to determine a safe dose of the ATLCAR.CD30 cells that can be given to subjects after undergoing an autologous transplant. This is the first step in determining whether giving ATLCAR.CD30 cells to others with lymphoma in the future will help them. The researchers also want to find out what side effects patients will have after they receive the ATLCAR.CD30 cells post-transplant. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on your cancer and how long they will survive in your body.

Conditions

Hodgkin Disease; Lymphoma; Lymphoma, Non-Hodgkin; Immune System Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Neoplasms; Neoplasms by Histologic Type

Keywords

CAR T cells; CD30; Lymphoma; T Lymphocytes

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Escalating Doses of Autologous Activated T Lymphocytes

  The Maximum tolerated dose was based on the rate of dose-limiting toxicity. Toxicity was classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0), and cytokine release syndrome (CRS). The number of subjects with dose-limiting toxicity was recorded.CTCAE Grade 1 Mild, Grade 2 Moderate, Grade 3, Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. Cytokine Release Syndrome (CRS) will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild Grade 2 - Moderate, Grade 3 - Severe (Aggressive Intervention): Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38oC, Hypotension requiring multiple vasopressors, Hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.

  6 weeks

Secondary Outcomes (3)

• To Measure the Survival of ATLCAR.CD30 in Vivo

  15 years

• To Estimate PFS After Infusion of ATLCAR.CD30 Post ASCT in Patients With CD30+ Lymphoma at High Risk for Relapse

  15 years

• Determine the Overall Survival After Infusion of ATLCAR.CD30

  15 years

Study Arms (1)

ATLCAR.CD30 cells

EXPERIMENTAL

Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10\^7 cells/m\^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10\^8/m\^2) given in the same trial. Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.

Drug: ATLCAR.CD30 cells

Interventions

ATLCAR.CD30 cells DRUG

Three dose levels will be evaluated: Group One, 2x10\^7 cells/m\^2 (maximum dose 5x10\^7 cells) Group Two, 1x10\^8 cells/m\^2 (maximum dose 2.5x10\^8 cells) Group Three, 2x10\^8 cells/m\^2 (maximum dose 5x10\^8 cells)

Also known as: CAR.CD30 T cells

ATLCAR.CD30 cells

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent.
• to 17 years of age for pediatric patients, ≥18 years of age for adults; NOTE: children will not be allowed to enroll in a dose cohort until a minimum of 2 adult subjects are enrolled and complete their DLT assessment follow-up at that dose level
• Diagnosis of recurrent HL with a treatment plan that will include high dose chemotherapy with/without total body irradiation and autologous cell transplantation
• NHL patients with ALK negative CD30+ anaplastic large-cell lymphomas, CD30+ ALCL regardless of ALK status, with chemotherapy-sensitive relapse, CD30+ high-risk DLBCL, CD30+ cutaneous T cell lymphoma, or CD30+ mycosis fungoides who are otherwise eligible for transplant, are eligible for this study
• CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30 cells); NOTE: CD30 + disease is defined as requiring documentation of CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
• Evidence of adequate organ function as defined by:
• The following is required prior to procurement (NOTE: labs do not need to be redrawn if they have already been performed as part of SOC pre-transplant work-up; Subject must be eligible to receive ASCT)
• Hgb ≥ 8.0g/dL
• Bilirubin ≤1.5 times the upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Serum creatinine ≤1.5 times ULN
• Cardiac and pulmonary function that is adequate for ASCT
• The following is required prior to infusion of ATLCAR.CD30 cells:
• Absolute neutrophil count (ANC) ≥500 cells/mm\^3 for 3 consecutive days; Note: ANC may be measured at the beginning and the end of a time frame expanding at least 3 days and does not need to be evaluated on each individual day AND
• Platelet count ≥25,000 cells/mm\^3 without transfusion over preceding 5 days Note: Platelets may be measured at the beginning and the end of a time frame expanding at least 5 days and does not need to be evaluated on each individual day AND

You may not qualify if:

• Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion.
• Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion
• History of hypersensitivity reactions to murine protein-containing products
• Pregnant or lactating
• Tumor in a location where enlargement could cause airway obstruction.
• Current use of systemic corticosteroids at doses ≥10mg/day prednisone or its equivalent; those receiving \<10mg/day may be enrolled at discretion of investigator
• Active infection with HIV, HTLV, HBV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) . Active infection is defined as not being well controlled on therapy (Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody, negative for Hepatitis B surface antigen, or negative for HCV antibody or HCV viral load).

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• Grover NS, Hucks G, Riches ML, Ivanova A, Moore DT, Shea TC, Seegars MB, Armistead PM, Kasow KA, Beaven AW, Dittus C, Coghill JM, Jamieson KJ, Vincent BG, Wood WA, Cheng C, Morrison JK, West J, Cavallo T, Dotti G, Serody JS, Savoldo B. Anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation in patients with high-risk CD30+ lymphoma: a phase 1 study. Lancet Haematol. 2024 May;11(5):e358-e367. doi: 10.1016/S2352-3026(24)00064-4. Epub 2024 Mar 28.

  PMID: 38555923 DERIVED

Related Links

• UNC Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma; Lymphoma, Non-Hodgkin; Immune System Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Neoplasms; Neoplasms by Histologic Type

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Melahat Canter
• Organization: UNC Lineberger Comprehensive Cancer Center

Melahat_Canter@med.unc.edu

919-962-0000

Study Officials

• Natalie Grover, MD

  Clinical Director of Cellular Therapy Program

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: January 17, 2016
• First Posted: January 26, 2016
• Study Start: June 7, 2016
• Primary Completion: January 15, 2021
• Study Completion (Estimated): January 1, 2037
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)