Phase I Study of Relapsed CD30 Expressing Lymphoma Treated With CD30 CAR T Cells (RELY-30)
The subject has a type of lymph gland cancer called 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. 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 with germs. Both antibodies and T cells have been used to treat patients with cancers; they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to test whether these genetically modified T cells given after chemotherapy will be more effective at killing cancer cells. The gene that will be put into the T cells 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 receptor-activated T cells (CD30.CAR T cells) seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown. Several studies suggest that the infused T cells need room to be able to multiply and grow to accomplish their functions, and that this may not happen if there are too many other T cells in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of circulating T cells prior to the CD30.CAR T cells infusion. This is called lymphodepletion CD30.CAR T cells have previously been studied in lymphoma patients.
• Diagnosis of relapsed/refractory HL or NHL.
• CD30 positive tumor as assayed in a CLIA certified pathology laboratory (result can be pending at this time)
• Hgb ≥ 7.0 (may be a transfused value)
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
• Karnofsky or Lansky score of \> 60%
• Diagnosis of relapsed/refractory HL or NHL.
• CD30-positive tumor as assayed in a CLIA certified pathology laboratory.
• Age 16 to 75 for the first three patients on a dose level; thereafter, if no DLT, patients aged 12 to 75 can be treated on that dose level.
• Bilirubin 1.5 times or less than the upper limit of normal.
• AST 3 times or less than the upper limit of normal.
• Estimated GFR \> 70 mL/min.
• Pulse oximetry of \> 90% on room air
• EKG shows no significant arrhythmias
• Karnofsky or Lansky score of \> 60%.
⁃ Available autologous T cells with greater than or equal to 15% expression of CD30CAR determined by flow-cytometry.
⁃ Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.
⁃ Adequate pulmonary function with FEV1, FVC and DLCO (or DLCO/VA, as clinically appropriate) greater than or equal to 50% of expected corrected for hemoglobin.
⁃ Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
⁃ Informed consent explained to, understood by and signed by patient or guardian.