Administration of T Lymphocytes for Prevention of Relapse of Lymphomas

This is an interventional treatment trial for Hodgkin Disease focused on measuring CAR T cells, CD30, Lymphoma, T Lymphocytes Read More

Inclusion Criteria:

• Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent.
• 3 to 17 years of age for pediatric patients, ≥18 years of age for adults; NOTE: children will not be allowed to enroll in a dose cohort until a minimum of 2 adult subjects are enrolled and complete their DLT assessment follow-up at that dose level
• Diagnosis of recurrent HL with a treatment plan that will include high dose chemotherapy with/without total body irradiation and autologous cell transplantation
• NHL patients with ALK negative CD30+ anaplastic large-cell lymphomas, CD30+ ALCL regardless of ALK status, with chemotherapy-sensitive relapse, CD30+ high-risk DLBCL, CD30+ cutaneous T cell lymphoma, or CD30+ mycosis fungoides who are otherwise eligible for transplant, are eligible for this study
• 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 is defined as requiring documentation of CD30 expression by immunohistochemistry based on the institutional hematopathology standard.

• Evidence of adequate organ function as defined by:

  • The following is required prior to procurement (NOTE: labs do not need to be redrawn if they have already been performed as part of SOC pre-transplant work-up; Subject must be eligible to receive ASCT)

    • Hgb ≥ 8.0g/dL
    • Bilirubin ≤1.5 times the upper limit of normal (ULN)
    • AST ≤ 3 times ULN
    • Serum creatinine ≤1.5 times ULN
    • Cardiac and pulmonary function that is adequate for ASCT

  • The following is required prior to infusion of ATLCAR.CD30 cells:

    • Absolute neutrophil count (ANC) ≥500 cells/mm^3 for 3 consecutive days; Note: ANC may be measured at the beginning and the end of a time frame expanding at least 3 days and does not need to be evaluated on each individual day AND
    • Platelet count ≥25,000 cells/mm^3 without transfusion over preceding 5 days Note: Platelets may be measured at the beginning and the end of a time frame expanding at least 5 days and does not need to be evaluated on each individual day AND
    • Hg ≥8g/dL without transfusion support over preceding 5 days Note: Hg may be measured at the beginning and the end of a time frame expanding at least 3 days and does not need to be evaluated on each individual day
    • Bilirubin ≤1.5 times the upper limit of normal (ULN)
    • AST ≤ 3 times ULN
    • Serum creatinine ≤1.5 times ULN
    • Pulse oximetry of > 90% on room air
• Imaging results from within 60 days prior to transplant (used as baseline measure for documentation of disease status). Note: Results may be obtained at a time point greater than 30 days from transplant if obtained per the patient's standard of care and with prior sponsor approval.
• Negative serum pregnancy test within 72 hours prior to procurement and again 72 hours prior to infusion
• Karnofsky or Lansky score of > 60%
• Considered at high risk for relapse as defined by: The presence of ≥ 1 of the following: failure to achieve CR post initial treatment; relapsed disease with an initial remission duration of <12 months; or extranodal involvement at the start of pre-transplant salvage therapy
• Subjects must have autologous transduced activated T cells that meet the Certificate of Analysis (CoA) acceptance criteria
• 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. The male partner of WOCBP subjects enrolled into the trial should be instructed to use a condom by their female partner enrolled in the trial.

Exclusion Criteria:

• Received any investigational agents or received any tumor vaccines within the previous six weeks prior to cell infusion.
• Received anti-CD30 antibody-based therapy within the previous 4 weeks prior to cell infusion
• History of hypersensitivity reactions to murine protein-containing products
• Pregnant or lactating
• Tumor in a location where enlargement could cause airway obstruction.
• Current use of systemic corticosteroids at doses ≥10mg/day prednisone or its equivalent; those receiving <10mg/day may be enrolled at discretion of investigator
• Active infection with HIV, HTLV, HBV, 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) . Active infection is defined as not being well controlled on therapy (Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody, negative for Hepatitis B surface antigen, or negative for HCV antibody or HCV viral load).