Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL

NCT02690545 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LCCC1532-ATL
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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 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. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of 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 it is now joined to the T cells. 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 establish a safe dose of ATLCAR.CD30 cells to infuse after lymphodepleting chemotherapy and to estimate the number patients whose cancer does not progress for two years after ATLCAR.CD30 administration. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on the patient's cancer.

Conditions

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 (3)

• Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion with bendamustine in adult patients

  Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE

  6 weeks

• Number of participants with adverse events as a measure of safety and tolerability of ATLCAR.CD30 cells to establish a safe dose after lymphodepletion after lymphodepletion with bendamustine and fludarabine in pediatric patients

  Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE

  6 weeks

• 2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL.

  PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a results of any cause per the Lugano classification.

  2 years

Secondary Outcomes (16)

• 2 year overall survival (OS) after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL.

  2 years

• 2 year overall survival (OS) after administration of ATLCAR.CD30 transduced ATl following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL

  2 years

• 2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ in adult patients with CD30+ refractory/relapsed HL and NHL.

  2 years

• 2 year progression free survival after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL.

  2 years

• Objective response rate as defined by the Lugano Classification for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL

  6 weeks

Study Arms (1)

ATLCAR.CD30 cells

EXPERIMENTAL

Phase Ib: In adults, and separately, in children, two doses will be investigated 1x10\^8 cells/m2 and 2x10\^8 cells/m\^2. The study team will run two independent dose-escalation sequences, one for adults and another one for children. The study team plans to use the 3+3 design and start with a low dose of 1x10\^8 cells/m2. If there are no DLT in first 3 patients, the study team will go up to the dose of 2 x 10\^8 cells/m2. If there is toxicity in 1/3 patients in the initial cohort, the study team would expand to enroll up to 6 patients. If there are dose limiting toxicities (DLT) at the dose of 2 x 10\^8 cells/m\^2, the study team will initially decrease the dose to an intermediate dose of 1.5 x 10\^8 cells/m\^. Phase II: The study team planning to enroll 31 patients to contribute data. Sequential boundary will be used to monitor DLT rate.

Biological: ATLCAR.CD30 cells

Interventions

ATLCAR.CD30 cells BIOLOGICAL

For Phase Ib, in adults and separately in children, two doses will be investigated: 1x10\^8 cells/m\^2 and 2x10\^8 cells/m\^2. Phase II patients will receive the dose level decided upon in Phase I.

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 the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form for procurement
• Ages 3 to 17 years of age for pediatric subjects (weight must be ≥10kg), and for adults ages ≥18 years of age
• Diagnosis of recurrent HL or NHL in subjects who have failed \>2 prior treatment regimens. Subjects relapsed after autologous or allogeneic stem cell 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 requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
• Karnofsky or Lansky score of \>60% (Karnofsky for ≥16 years old and Lansky for \<16 years old)
• Evidence of adequate organ function as defined by:
• Hemoglobin ≥ 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment)
• Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert's Syndrome
• AST ≤ 3 × ULN
• Serum creatinine ≤ 1.5 × ULN
• For subjects \<18 years old use the following table for serum creatinine requirements:
• Maximum Serum Creatinine (mg/dL) Age (years) Male Female 3 to \<6 ≤0.8 ≤0.8 6 to \<10 ≤1.0 ≤1.0 10 to \<13 ≤1.2 ≤1.2 13 to \<16 ≤1.5 ≤1.4 ≥16 and \<18 ≤1.7 ≤1.4
• Negative serum pregnancy test in females within 72 hours prior to procurement or documentation that the subject is post-menopausal or premenarchal.
• Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for \>1 year.
• Postmenopausal status must be confirmed with documentation of absence of menses for \>1 year.

You may not qualify if:

• Pregnant or lactating
• Tumor in a location where enlargement could cause airway obstruction
• Must not have an Active infection with human immunodeficiency virus (HIV), Hepatitis B Virus (HBV))or, Hepatitis C virus (HCV) (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused). Note: To meet eligibility subjects are required to have negative HIV antibody, negative for Hepatitis B surface antigen and negative for HCV antibody or viral load.
• Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guradian given a copy of informed consent form.
• CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to lymphodepletion); Note: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
• Prior to administration of lymphodepletion:
• Absolute neutrophil count (ANC) is \> 1.0 × 10\^9/L
• Platelet count \> 75 × 10\^9/L
• For Grade 4 neutropenia, Grade ≥3 febrile neutropenia, or Grade 4 thrombocytopenia, hold bendamustine until toxicity resolve to Grade ≤2
• For WOCBP negative serum pregnancy test within 72 hours prior to lymphodepletion.
• Imaging results from within 7 days (30 days in subjects with cutaneous T cell lymphoma) prior to lymphodepletion. Subjects who have received bridging chemotherapy must have imaging performed at least 3 weeks after most recent therapy (imaging does not need to be repeated if it is within 7 days prior to lymphodepletion).
• Karnofsky or Lansky score of \>60% (Karnofsky for pediatric subjects ≥16 years old and Lansky for \<16 years old).
• Available autologous transduced activated T cells that meet the Certificate of Analysis (CofA) acceptance criteria.
• Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded. WOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

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

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (3)

• Tschernia NP, Heiling H, Deal AM, Cheng C, Babinec C, Gonzalez M, Morrison JK, Dittus C, Dotti G, Beaven AW, Serody JS, Wood WA, Savoldo B, Grover NS. Patient-reported outcomes in CD30-directed CAR-T cells against relapsed/refractory CD30+ lymphomas. J Immunother Cancer. 2023 Aug;11(8):e006959. doi: 10.1136/jitc-2023-006959.

  PMID: 37527906 DERIVED

• Voorhees TJ, Zhao B, Oldan J, Hucks G, Khandani A, Dittus C, Smith J, Morrison JK, Cheng CJ, Ivanova A, Park S, Shea TC, Beaven AW, Dotti G, Serody J, Savoldo B, Grover N. Pretherapy metabolic tumor volume is associated with response to CD30 CAR T cells in Hodgkin lymphoma. Blood Adv. 2022 Feb 22;6(4):1255-1263. doi: 10.1182/bloodadvances.2021005385.

  PMID: 34666347 DERIVED

• Ramos CA, Grover NS, Beaven AW, Lulla PD, Wu MF, Ivanova A, Wang T, Shea TC, Rooney CM, Dittus C, Park SI, Gee AP, Eldridge PW, McKay KL, Mehta B, Cheng CJ, Buchanan FB, Grilley BJ, Morrison K, Brenner MK, Serody JS, Dotti G, Heslop HE, Savoldo B. Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2020 Nov 10;38(32):3794-3804. doi: 10.1200/JCO.20.01342. Epub 2020 Jul 23.

  PMID: 32701411 DERIVED

Related Links

• University of North Carolina (UNC) Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

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

Study Officials

• Anne Beaven, MD

  Director, UNC Lineberger Lymphoma Program

  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

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 24, 2016
• Study Start: August 26, 2016
• Primary Completion: December 16, 2025
• Study Completion (Estimated): November 4, 2039
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)