Phase Ib/II Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Relapsed/Refractory CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma
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.
⁃ 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.
⁃ 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.
⁃ Evidence of adequate organ function as defined by:
• Total bilirubin ≤1.5 × ULN, unless attributed to Gilbert's Syndrome
• AST ≤3 × ULN
• Serum creatinine ≤1.5 × ULN
• Pulse oximetry of \>90% on room air
• For subjects \<18 years old use 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
⁃ Karnofsky or Lansky score of \>60% (Karnofsky for ≥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.