Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL

Exclusion Criteria

• •Pregnant or lactating.
• •Tumor in a location where enlargement could cause airway obstruction.
• •Current use of systemic corticosteroids at doses ≥10mg prednisone daily or its equivalent; those receiving \<10mg daily may be enrolled at discretion of the Investigator.
• •Active infection with HIV, HTLV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) defined as not being well controlled on therapy. Subjects are required to have negative HIV antibody, negative HTLV1 and 2 antibody, and negative HCV antibody or viral load.
• •Active infection with 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.
• •Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years.
• •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.
• •Subject is not a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per Investigator's discretion.
• •Eligibility criteria to be met prior to procurement
• •Evidence of adequate organ function as defined by:
• •The following is required prior to procurement:
• •Hgb ≥ 8.0g/dL (transfusion independent for 2 weeks prior to enrollment)
• •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× ULN
• •AST ≤ 3 times ULN
• •Serum creatinine ≤1.5 times ULN or Creatinine Clearance (CrCl) \>60mL/min per Cockcroft and Gault
• •Pulse oximetry of \>90% on room air
• •Imaging results from within 120 days prior to procurement to assess presence of active disease (no tumor imaging is required prior to procurement for participants with active cutaneous lymphoma).
• •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.
• •Subject has no clinical indication of rapidly progressing disease in opinion of treating physician.
• •Subject has adequate cardiac function, defined as:
• •* No 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
• •Eligibility criteria to be met prior to lymphodepletion
• •Presence of active disease. Imaging results from 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).
• •Evidence of adequate organ function as defined by:
• •The following are required prior to lymphodepletion:
• •Adequate bone marrow function (ANC\>1000 cells/mm3 and platelets \>75,000/mm3). Subjects cannot have received platelet transfusion within 7 days of lymphodepletion.
• •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× ULN)
• •AST ≤ 3 times ULN
• •Serum creatinine ≤1.5 times ULN or Creatinine Clearance (CrCl) \>60mL/min per Cockcroft and Gault
• •Pulse oximetry of \> 90% on room air
• •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.
• •Subjects must have autologous transduced activated T-cells that meet the Certificate of Analysis (CofA) acceptance criteria.
• •Has not received any investigational agents or received any tumor vaccines within the previous six weeks prior to lymphodepletion.
• •Has not received anti-CD30 antibody-based therapy within the previous 4 weeks prior to lymphodepletion.
• •Has not received chemotherapy or radiation therapy within the previous 3 weeks 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. See http://medicine.iupui.edu/clinpharm/ddis/ for an updated list of strong inhibitors of CYP1A2. (This applies to subjects who receive bendamustine for lymphodepletion (required) up through 72 hours after the last dose of bendamustine).
• •Subjects who are HBV core antibody positive and HBV viral load negative prior to lymphodepletion must have initiated anti-HBV prophylaxis prior to lymphodepletion.
• •Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician.
• •Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per the investigator's discretion.
• •Eligibility criteria to be met prior to cell infusion after lymphodepletion
• •No evidence of uncontrolled infection or sepsis.
• •Evidence of adequate organ function as defined by:
• •1. Bilirubin ≤2 times the upper limit of normal (ULN) unless attributed to Gilbert's syndrome
• •2. AST ≤5 times ULN
• •3. ALT ≤5 times ULN
• •4. Serum creatinine ≤3 times ULN
• •5. Pulse oximetry of \>90% on room air
• •* Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician.
• •* Subject is a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per the investigator's discretion.