Genetically Engineered Cells (ATLCAR.CD30.CCR4 CAR T Cells) for the Treatment of Relapsed or Refractory CD30 Positive Hodgkin Lymphoma

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative
• Age ≥ 18 years at the time of consent
• Subject must have a diagnosis of classical Hodgkin lymphoma by World Health Organization (WHO) criteria
• Diagnosis of recurrent lymphoma in subjects who have failed ≥ 2 prior treatment regimens. * Subjects must have previously been treated with brentuximab vedotin and a checkpoint inhibitor unless contraindicated
• Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 3 months after the cell infusion therapy
• Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
• Subject is willing to undergo a biopsy prior to treatment, after CAR-T cell infusion, and at the time of progression, and the tumor is determined to be safe by the treating investigator for biopsy collection and the procedure would not be required to be performed in the operating room
• Subjects with history of intolerance to fludarabine or bendamustine will be excluded
• PRIOR TO PROCUREMENT: Written informed consent to undergo cell procurement explained to, understood by and signed by the subject or legally authorized representative; subject and/or legally authorized representative given a copy of informed consent form for cell procurement
• PRIOR TO PROCUREMENT: Karnofsky score of > 60%
• PRIOR TO PROCUREMENT: Subject has life expectancy of ≥ 12 weeks
• PRIOR TO PROCUREMENT: CD30+ disease documented by immunohistochemistry based on the institutional hematopathology standard
• PRIOR TO PROCUREMENT: Subject must not have an active infection with HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) (tests 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 be negative for HIV antibody, negative for hepatitis B surface antigen, negative for HCV antibody or HCV viral load. 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
• PRIOR TO PROCUREMENT: Subject must not be using 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. 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
• PRIOR TO PROCUREMENT: Subjects with a history of intolerance to fludarabine or bendamustine will be excluded
• PRIOR TO PROCUREMENT: Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
• PRIOR TO PROCUREMENT: Imaging results available from within 120 days prior to procurement to confirm presence of active disease
• PRIOR TO PROCUREMENT: Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician
• PRIOR TO PROCUREMENT: Subject has an ejection fraction cut-off of ≥ 35% as determined by echocardiogram
• PRIOR TO PROCUREMENT: Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Platelets ≥ 75 x 10^9/L (after 1 week of not requiring a transfusion) (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Serum Creatinine ≤ 2 x upper limit of normal (ULN) (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Bilirubin ≤ 1.5 x upper limit of normal (ULN) Subjects with Gilbert’s syndrome may be enrolled despite a total bilirubin level > 1.5 milligrams/deciliter (mg/dL) if their conjugated bilirubin is < 1.5 x ULN (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Aspartate aminotransferase (AST) ≤ 3 x ULN (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Alanine aminotransferase (ALT) ≤ 3 x ULN (within 7 days of cell procurement)
• PRIOR TO PROCUREMENT: Pulse oximetry ≥ 90% on room air (within 7 days of cell procurement)
• PRIOR TO LYMPHODEPLETION: Written informed consent to undergo therapy with ATLCAR.CD30.CCR4 cells explained to, understood by and signed by the subject or legally authorized representative; subject/legally authorized representative given a copy of informed consent form
• PRIOR TO LYMPHODEPLETION: Karnofsky score of > 60%
• PRIOR TO LYMPHODEPLETION: No major surgery within 28 days to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject has not received any investigational agents or any tumor vaccines within 3 weeks prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject has not received chemotherapy or radiation therapy within the previous 3 weeks prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subject has not received anti-CD30 antibody-based therapy within the previous 4 weeks prior to lymphodepletion
• 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. See http://medicine.iupui.edu/clinpharm/ddis/ for an updated list of strong inhibitors of CYP1A2 (This applies to subjects for lymphodepletion [required] up through 72 hours after the last dose of bendamustine)
• PRIOR TO LYMPHODEPLETION: 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: Subjects must not be using 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. 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
• PRIOR TO LYMPHODEPLETION: Imaging results available from within 14 days prior to lymphodepletion to confirm the presence of measurable disease per Lugano Criteria. Imaging must occur at least 3 weeks after most recent therapy, including any bridging therapy (used as baseline and to document measurable disease)
• PRIOR TO LYMPHODEPLETION: Subject must have available ATLCAR.CD30.CCR4 cells that meet the Certificate of Analysis acceptance criteria
• PRIOR TO LYMPHODEPLETION: Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Platelets ≥ 75 x 10^9/L at least 1 week following last transfusion (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Serum creatinine ≤ 2 x ULN (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Bilirubin ≤ 1.5 x 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. (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Aspartate aminotransferase (AST) ≤ 3 x ULN (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Alanine aminotransferase (ALT) ≤ 3 x ULN (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Pulse oximetry ≥ 90% on room air (within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for female participants of childbearing potential. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• PRIOR TO LYMPHODEPLETION: Subject is a good candidate for ATLCAR.CD30.CCR4 cell therapy, per treating oncologist’s discretion
• PRIOR TO CELL PRODUCT ADMINISTRATION: Subject has no evidence of uncontrolled infection or sepsis
• PRIOR TO CELL PRODUCT ADMINISTRATION: Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 cells per the clinical investigator’s discretion
• PRIOR TO CELL PRODUCT ADMINISTRATION: No new clinical findings that in the opinion of the treating physician would jeopardize the subject’s safety