CD30 Receptor-Activated T-cells in Treating Patients with Relapsed or Refractory CD30+ Hodgkin Lymphoma or Non-Hodgkin Lymphoma

Inclusion Criteria

• PRIOR TO CELL PROCUREMENT: Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guardian given a copy of informed consent form for procurement
• PRIOR TO CELL PROCUREMENT: Ages 3 to 17 years of age for pediatric subjects (weight must be >= 10kg), or for adults >= 18 years of age
• PRIOR TO CELL PROCUREMENT: 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
• PRIOR TO CELL PROCUREMENT: 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
• PRIOR TO CELL PROCUREMENT: Karnofsky or Lansky score of > 60% (Karnofsky for >= 16 years old and Lansky for < 16 years old)
• PRIOR TO CELL PROCUREMENT: Hemoglobin (Hgb) >= 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment)
• PRIOR TO CELL PROCUREMENT: Total bilirubin =< 1.5 times the upper limit of normal (ULN), unless attributed to Gilbert’s syndrome
• PRIOR TO CELL PROCUREMENT: Aspartate aminotransferase (AST) =< 3 times ULN
• PRIOR TO CELL PROCUREMENT: Serum creatinine =< 1.5 times ULN
• PRIOR TO CELL PROCUREMENT: For subjects < 18 years old use the following table for serum creatinine requirements: * Age (years): Maximum serum creatinine (mg/dL) * 3 to < 6: =< 0.8 (male and female) * 6 to < 10: =< 1.0 (male and female) * 10 to < 13: =< 1.2 (male and female) * 13 to < 16: =< 1.5 (male), =< 1.4 (female) * >= 16 and < 18: =< 1.7 (male), =< 1.4 (female)
• PRIOR TO CELL PROCUREMENT: Negative serum pregnancy test in females within 72 hours prior to procurement or documentation that the subject is post-menopausal or premenarchal
• PRIOR TO CELL PROCUREMENT: 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; the two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy; WOCBP subjects will also be instructed to tell their male partners to use a condom * Postmenopausal status must be confirmed with documentation of absence of menses for > 1 year
• PRIOR TO LYMPHODEPLETION: Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guardian given a copy of informed consent form
• PRIOR TO LYMPHODEPLETION: 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 LYMPHODEPLETION: Absolute neutrophil count (ANC) is > 1.0 x 10^9/L
• PRIOR TO LYMPHODEPLETION: Platelet count > 75 x 10^9/L
• PRIOR TO LYMPHODEPLETION: For grade 4 neutropenia, >= grade 3 febrile neutropenia, or grade 4 thrombocytopenia, hold bendamustine until toxicity resolve to =< grade 2
• PRIOR TO LYMPHODEPLETION: For WOCBP negative serum pregnancy test within 72 hours prior to lymphodepletion
• 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)
• PRIOR TO LYMPHODEPLETION: Karnofsky or Lansky score of > 60% (Karnofsky for pediatric subjects >= 16 years old and Lansky for < 16 years old)
• PRIOR TO LYMPHODEPLETION: Available autologous transduced activated T-cells that meet the Certificate of Analysis (CofA) acceptance criteria
• PRIOR TO LYMPHODEPLETION: 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; the two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy; WOCBP subjects will also be instructed to tell their male partners to use a condom; post-menopausal status must be confirmed with documentation of absence of menses for > 1 year
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Total bilirubin =< 1.5 times the upper limit of normal (ULN), unless attributed to Gilbert’s syndrome
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: AST =< 3 times ULN
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Serum creatinine =< 1.5 times ULN
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Pulse oximetry of > 90% on room air
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: For subjects < 18 years old use the following table for serum creatinine requirements: * Age (years): Maximum serum creatinine (mg/dL) * 3 to < 6: =< 0.8 (male and female) * 6 to < 10: =< 1.0 (male and female) * 10 to < 13: =< 1.2 (male and female) * 13 to < 16: =< 1.5 (male), =< 1.4 (female) * >= 16 and < 18: =< 1.7 (male), =< 1.4 (female)
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Karnofsky or Lansky score of > 60% (Karnofsky for >= 16 years old and Lansky for < 16 years old)
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: 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; the two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy; WOCBP subjects will also be instructed to tell their male partners to use a condom; post-menopausal status must be confirmed with documentation of absence of menses for > 1 year
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Karnofsky or Lansky score of > 60% (Karnofsky for >= 16 years old and Lansky for <16 years old)
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): WOCBP must be willing to use 2 methods of birth control or be surgically sterile , or abstain from heterosexual activity for the course of the study, or 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. The two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. WOCBP subjects will also be instructed to tell their male partners to use a condom
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Must not be pregnant or lactating
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Must not have tumor in a location where enlargement could cause airway obstruction
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Subjects must have imaging results confirming active disease from within 30 days prior to lymphodepletion with the exception of cutaneous lymphoma subjects who do not need to repeat scans prior to the second cell infusion if baseline scans showed lymph nodes =< 1.5 cm
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Must not have current use of systemic corticosteroids at doses >=10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of the investigator
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): ANC > 1.0 x 10^9/L
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Platelets > 75 x 10^9/L
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Total bilirubin =< 1.5 x ULN, unless attributed to Gilbert’s syndrome
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): AST =< 3 x ULN
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Serum creatinine =< 1.5 x ULN
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Pulse oximetry of > 90% on room air
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): For subjects < 18 years old use the following table for serum creatinine requirements: * Age (years): Maximum serum creatinine (mg/dL) * 3 to < 6: =< 0.8 (male and female) * 6 to < 10: =< 1.0 (male and female) * 10 to < 13: =< 1.2 (male and female) * 13 to < 16: =< 1.5 (male), =< 1.4 (female) * >= 16 and < 18: =< 1.7 (male), =< 1.4 (female)
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Negative serum pregnancy test within 72 hours prior to lymphodepletion or documentation that the subject is post-menopausal or premenarchal. Post-menopausal status must be confirmed with documentation of absence of menses for > 1 year or documentation of surgical menopause involving bilateral oophorectomy
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Subject cannot be on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites. (This applies to subjects who receive bendamustine for lymphodepletion (required) up through 72 hours after the last dose of bendamustine)
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Subject is a good candidate for treatment with ATLCAR.CD30 per the investigator’s discretion
• PRIOR TO LYMPHODEPLETION FOR SECOND INFUSION (OPTIONAL): Subject must not have undergone bridging chemotherapy (or other anti-cancer therapies, which are not mandated by the protocol) prior to lymphodepletion for the second infusion
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): No evidence of uncontrolled infection or sepsis
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Subject must not have undergone bridging chemotherapy (or other anti-cancer therapies, which are not mandated by the protocol) prior to the second infusion
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Total bilirubin =< 2 X ULN, unless attributed to Gilbert’s syndrome
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): AST =< 3 X ULN
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): ALT =< 3 x ULN
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Serum creatinine =< 1.5 x ULN
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Pulse oximetry of > 90% on room air
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): For subjects < 18 years old use following table for serum creatinine requirements: * Age (years): Maximum serum creatinine (mg/dL) * 3 to < 6: =< 0.8 (male and female) * 6 to < 10: =< 1.0 (male and female) * 10 to < 13: =< 1.2 (male and female) * 13 to < 16: =< 1.5 (male), =< 1.4 (female) * >= 16 and < 18: =< 1.7 (male), =< 1.4 (female)
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Subject is a good candidate for treatment with ATLCAR.CD30 per the investigator’s discretion
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): If subjects have had positive Hepatitis B core antibody testing at baseline, they must not have had re-activation of the hepatitis B virus since baseline testing (i.e., they will be excluded if any of their hepatitis B viral load testing is positive up until the point of eligibility determination for re-infusion)
• ELIGIBILITY CRITERIA PRIOR TO SECOND INFUSION (OPTIONAL): Subject must not be pregnant or lactating

Exclusion Criteria

• PRIOR TO CELL PROCUREMENT: Pregnant or lactating
• PRIOR TO CELL PROCUREMENT: Tumor in a location where enlargement could cause airway obstruction
• PRIOR TO CELL PROCUREMENT: 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.
• PRIOR TO LYMPHODEPLETION: Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell lymphodepletion
• PRIOR TO LYMPHODEPLETION: Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell lymphodepletion
• PRIOR TO LYMPHODEPLETION: Received chemotherapy within the previous 3 weeks prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject has rapidly progressive disease, per treating oncologist’s discretion
• PRIOR TO LYMPHODEPLETION: Subject is not a good candidate for CAR-T cell therapy, per treating oncologist’s discretion
• PRIOR TO LYMPHODEPLETION: Pregnant or lactating
• PRIOR TO LYMPHODEPLETION: Tumor in a location where enlargement could cause airway obstruction
• PRIOR TO LYMPHODEPLETION: Current use of systemic corticosteroids at doses equivalent of >= 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator; inhaled steroids are allowed * For pediatric subjects, physiologic replacement hydrocortisone at doses 6-12 mg/m^2/day is allowed; equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10mg prednisone per day; inhaled steroids are allowed
• PRIOR TO LYMPHODEPLETION: Subjects on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites (This applies to subjects who receive bendamustine for lymphodepletion (required) up through 72 hours after the last dose of bendamustine.)
• PRIOR TO LYMPHODEPLETION: Active infection with HIV, HBV, HCV (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused), Subjects are required to have negative HIV antibody negative for Hepatitis B surface antigen, and negative HCV antibody or viral load
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Tumor in a location where enlargement could cause airway obstruction
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subject has rapidly progressive disease, per treating oncologist’s discretion
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subject is not a good candidate for CAR-T cell therapy, per treating oncologist’s discretion
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Current use of systemic corticosteroids at doses >= 10 mg prednisone daily or its equivalent; those receiving < 10 mg daily may be enrolled at discretion of investigator; inhaled steroids are allowed * For pediatric subjects, physiologic replacement hydrocortisone at doses 6-12 mg/m^2/day is allowed; equivalently dosed alternative steroids are allowed at discretion of investigator, though not to exceed 10 mg prednisone per day; inhaled steroids are allowed
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Active infection with HIV, HBV, HCV (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused) Subjects are required to be negative for HIV antibody, negative for Hepatitis B surface antigen, and negative for HCV antibody or viral load
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subjects who are positive for hepatitis B surface antigen are excluded; subjects who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked; these subjects will be excluded if their viral load is positive at baseline; subjects who are core antibody positive and viral load negative at baseline will be considered eligible; these subjects must be receiving antiviral prophylaxis initiated prior to lymphodepletion
• PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Subject must not be pregnant or lactating within 7 days of infusion