ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 in Treating Patients with Relapsed or Refractory CD30+ Hodgkin Lymphoma or Cutaneous T-cell Lymphoma

Inclusion Criteria

• PRIOR TO CELL PROCUREMENT: Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. Subjects or their legally authorized representative must sign a consent to undergo cell procurement.
• PRIOR TO CELL PROCUREMENT: Adults >= 18 years of age.
• PRIOR TO CELL PROCUREMENT: Subjects must have one of the following diagnoses by World Health Organization (WHO) criteria: * Classic Hodgkin lymphoma * Mycosis fungoides * Sezary syndrome * Primary cutaneous CD30 positive T cell lymphoproliferative disorder including lymphomatoid papulosis or primary cutaneous anaplastic large cell lymphoma * B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classic Hodgkin lymphoma (grey zone lymphoma)
• PRIOR TO CELL PROCUREMENT: Diagnosis of recurrent lymphoma in subjects who have failed >= 2 prior treatment regimens. * These prior treatment regimens must include brentuximab vedotin. * If the subject has Hodgkin lymphoma, the subject must have either failed autologous transplant or must not be eligible for autologous transplant. * If the subject has grey zone lymphoma, the subject must have failed an anthracycline containing regimen unless the subject was not previously a candidate for anthracycline. * 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.CCR4 and ATLCAR.CD30 cells). * NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
• PRIOR TO CELL PROCUREMENT: Karnofsky score of > 60%.
• PRIOR TO CELL PROCUREMENT: For Subjects in the Expansion Cohort: Willing to undergo biopsy following the cell infusion. A biopsy may be required (i.e., considered mandatory) in subjects receiving both cellular products if the investigator determines the tumor site is easily accessible (e.g., palpable tumor). If the investigator feels that the biopsy would be difficult to obtain or poses a high degree of risk to the subject, it may be deferred.
• PRIOR TO CELL PROCUREMENT: Women of childbearing potential (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, 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.
• PRIOR TO CELL PROCUREMENT: Subjects with prior or concurrent malignancies of the same or different tumor type whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational drug are eligible for enrollment at the discretion of the treating physician.
• PRIOR TO CELL PROCUREMENT: Subjects must not be pregnant or lactating.
• PRIOR TO CELL PROCUREMENT: Subjects must not be using systemic corticosteroids at doses >= 10mg prednisone daily or its equivalent; those receiving < 10mg daily may be enrolled at discretion of the investigator.
• PRIOR TO CELL PROCUREMENT: Subjects must not have an active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) (can be pending at the time of cell procurement; only subjects meeting the criteria as so described will be infused) defined as not being well controlled on therapy. Subjects are required to have negative HIV antibody, and negative HCV antibody or viral load.
• PRIOR TO CELL PROCUREMENT: Subjects must not have an active infection with hepatitis B virus (HBV). Subjects are required to have a negative hepatitis B surface antigen. In addition, subjects must either have core antibody negative HBV (results can be pending at the time of cell procurement) OR if a subject is hepatitis B core antibody positive, they 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.
• PRIOR TO CELL PROCUREMENT: Subjects must not have a history of intolerance to fludarabine. Subjects with an intolerance to bendamustine may be allowed to enroll at the discretion of the clinical investigator if he/she thinks that the subject is a candidate for lymphodepletion with cyclophosphamide and fludarabine.
• PRIOR TO CELL PROCUREMENT: Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per investigator’s discretion.
• PRIOR TO PROCUREMENT: Hemoglobin (Hgb) >= 8.0 g/dL (transfusion independent for 2 weeks prior to enrollment).
• PRIOR TO PROCUREMENT: Bilirubin =< 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 1.5 mg/dL if their conjugated bilirubin is < 1.5 x ULN).
• PRIOR TO PROCUREMENT: Aspartate aminotransferase (AST) =< 3 times ULN.
• PRIOR TO PROCUREMENT: Serum creatinine =< 1.5 times ULN.
• PRIOR TO PROCUREMENT: Creatinine clearance (CrCl) > 60mL/min per Cockcroft and Gault.
• PRIOR TO PROCUREMENT: Pulse oximetry of > 90% on room air.
• PRIOR TO CELL PROCUREMENT: Subject must have active disease by imaging, skin and/or blood assessment. Imaging results must be obtained within 120 days prior to procurement to assess presence of active disease (no tumor imaging is required prior to procurement for participants with cutaneous lymphoma).
• PRIOR TO CELL PROCUREMENT: Negative serum pregnancy test within 72 hours prior to procurement or documentation that the subject is post-menopausal. 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 CELL PROCUREMENT: Subject has no clinical indication of rapidly progressing disease in opinion of treating physician.
• PRIOR TO CELL PROCUREMENT: Subject has adequate cardiac function, defined as: * No electrocardiogram (ECG) evidence of acute ischemia. * No ECG evidence of active, clinically significant conduction system abnormalities. * Prior to study entry, any ECG abnormality at screening not felt to put the subject at risk has to be documented by the investigator as not medically significant. * No uncontrolled angina or severe ventricular arrhythmias. * No clinically significant pericardial disease. * No history of myocardial infarction within the last 6 months prior to infusion. * No class 3 or higher New York Heart Association congestive heart failure.
• PRIOR TO LYMPHODEPLETION: Written informed consent to enroll in the CAR T-cell therapy trial must be obtained prior to lymphodepletion.
• PRIOR TO LYMPHODEPLETION: Presence of active disease by imaging and/or cutaneous involvement. Imaging must be performed within 7 days prior to lymphodepletion to confirm presence of active disease. 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: Adequate bone marrow function (absolute neutrophil count (ANC) > 1000 cells/mm^3 and platelets > 50,000/mm^3). Subjects cannot have received platelet transfusion within 7 days of lymphodepletion.
• PRIOR TO LYMPHODEPLETION: Bilirubin =< 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's syndrome may be treated despite a total bilirubin level > 1.5 mg/dL if their conjugated bilirubin is < 1.5 x ULN).
• PRIOR TO LYMPHODEPLETION: AST =< 3 times ULN.
• PRIOR TO LYMPHODEPLETION: Serum creatinine =< 2 times ULN.
• PRIOR TO LYMPHODEPLETION: Creatinine clearance (CrCl) > 60 mL/min per Cockcroft and Gault.
• PRIOR TO LYMPHODEPLETION: Pulse oximetry of > 90% on room air.
• PRIOR TO LYMPHODEPLETION: Negative serum pregnancy test within 72 hours prior to lymphodepletion or documentation that the subject is post-menopausal. 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: Subjects must have autologous transduced activated T-cells that meet the Certificate of Analysis (CofA) acceptance criteria.
• PRIOR TO LYMPHODEPLETION: Has not received any investigational agents or received any tumor vaccines within the previous six weeks prior to lymphodepletion.
• PRIOR TO LYMPHODEPLETION: Has not received anti-CD30 antibody-based therapy within the previous 4 weeks prior to lymphodepletion.
• PRIOR TO LYMPHODEPLETION: Has not received chemotherapy or radiation therapy within the previous 3 weeks prior to lymphodepletion.
• PRIOR TO LYMPHODEPLETION: Subjects 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: Subjects must not have an active infection with HIV, HBV, or HCV. Subjects who are HBV core antibody positive and HBV viral load negative prior to lymphodepletion must have initiated anti-HBV prophylaxis prior to lymphodepletion.
• PRIOR TO LYMPHODEPLETION: Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician.
• PRIOR TO LYMPHODEPLETION: Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per the investigator’s discretion.
• PRIOR TO LYMPHODEPLETION: Karnofsky score of > 60%.
• PRIOR TO LYMPHODEPLETION: For Subjects in the Expansion Cohort: Willing to undergo biopsy following the cell infusion. A biopsy may be required (i.e., considered mandatory) in subjects receiving both cellular products if the Investigator determines the tumor site is easily accessible (e.g., palpable tumor). If the Investigator feels that the biopsy would be difficult to obtain or poses a high degree of risk to the subject, it may be deferred.
• PRIOR TO LYMPHODEPLETION: Subjects must not be using systemic corticosteroids at doses >= 10mg prednisone daily or its equivalent; those receiving < 10mg daily may be treated at discretion of the investigator.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: No evidence of uncontrolled infection or sepsis.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: Bilirubin =< 2 times the upper limit of normal (ULN) unless attributed to Gilbert’s syndrome.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: AST =< 5 times ULN.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: Alanine aminotransferase (ALT) =< 5 times ULN.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: Serum creatinine =< 3 times ULN.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: Pulse oximetry of > 90% on room air.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician.
• PRIOR TO CELL INFUSION AFTER LYMPHODEPLETION: Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per the investigator’s discretion.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Karnofsky score > 60%
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: 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 OPTIONAL REINFUSION: Must not be pregnant or lactating.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Must not have tumor in a location where enlargement could cause airway obstruction.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: 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 OPTIONAL REINFUSION: ANC > 1000 cells/mm^3. Subjects cannot have received platelet transfusion within 7 days of lymphodepletion. Note: Subjects may receive a second infusion without prior lymphodepletion or with a 25-50% dose reduction in bendamustine if they meet all other eligibility criteria at the time of infusion.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Platelets > 50,000/mm^3. Subjects cannot have received platelet transfusion within 7 days of lymphodepletion. Note: Subjects may receive a second infusion without prior lymphodepletion or with a 25-50% dose reduction in bendamustine if they meet all other eligibility criteria at the time of infusion.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Bilirubin =< 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level > 1.5 mg/dL if their conjugated bilirubin is < 1.5 x ULN)
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: AST =< 3 times ULN.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Serum creatinine =< 2 times ULN.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Creatinine clearance (CrCl) > 60 mL/min per Cockcroft and Gault
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Pulse oximetry of > 90% on room air.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Negative serum pregnancy test within 72 hours prior to lymphodepletion or documentation that the subject is post-menopausal. 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 OPTIONAL REINFUSION: Subjects 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.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with ATLCAR.CD30 per the investigator’s discretion.
• PRIOR TO LYMPHODEPLETION FOR OPTIONAL REINFUSION: Subject must have a negative human anti-mouse antibodies (HAMA) test.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: No evidence of uncontrolled infection or sepsis.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: Bilirubin =< 2 times the upper limit of normal (ULN) unless attributed to Gilbert’s syndrome.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: AST =< 3 times ULN.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: ALT =< 3 times ULN.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: Serum Creatinine =< 3 times ULN.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: Pulse oximetry of > 90% on room air.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician.
• PRIOR TO INFUSION OF OPTIONAL REINFUSION: Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with ATLCAR.CD30 per the investigator’s discretion.