CD30 CAR T-cells Post AutoHSCT for Poor-risk Hodgkin Lymphoma

MAC-CAR: A Phase 1B/II Trial of Myeloablative Conditioning and Autologous Stem Cell Transplantation Followed by Autologous CD30+ CAR T Cells in Children, Adolescents and Young Adults With Poor-Risk Classical Hodgkin Lymphoma (cHL)

Patients with poor risk classical Hodgkin Lymphoma (cHL) will undergo myeloablative chemotherapy (MAC) with autologous stem cell transplantation (AutoHSCT) and subsequently receive autologous CD30+ CAR T-cells.

Eligible patients will be screened for study entry and proceed to cell procurement at local sites with collection of peripheral blood mononuclear cells (PBMC) for CD30+ CAR T-cell manufacturing at UNC. Patients will then have autologous stem cells collected (PBSC) and stored for future AutoHSCT.

After another screening for MAC+AutoHSCT, patients who meet criteria will receive BEAM conditioning followed by AutoHSCT. About 21-42 day after the autologous stem cell infusion, patients will receive their autologous CD30+ CAR T-cell infusion, if they meet subsequent pre CD30+ CAR T-cell eligibility criteria.

Inclusion Criteria:

• Age between ≥ 6 and ≤ 29.99 years at the time of consent.
• Lansky OR Karnofsky score of ≥ 60% (see Appendix VI)
• Disease Status: Confirmed diagnosis of CD30+ classical Hodgkin Lymphoma and meets eligibility to undergo ASCT. Must meet one of the following:

Induction failure Progressive disease Disease relapse (1st, 2nd or 3rd)

• Confirmatory re-biopsy of relapse/refractory/persistent CD30+ cHL prior to study entry.
• Risk Factors: Patient must meet 2 or more of the established risk factors:

Performance score (Karnofsky/Lansky) <;90% Time from diagnosis to first relapse of <1 year Extra nodal involvement at the time of relapse/progression High baseline metabolic tumor volume (MTV, >60mL) by 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) Chemo resistant disease (Deauville 4-5) after the first re-induction

Exclusion Criteria:

• not meeting the inclusion criteria