A Study for Patients with Large B-Cell Lymphoma Who have Completed Initial Therapy

This a randomized, open-label study is being conducted in patients diagnosed with large B-cell lymphoma who have completed initial therapy. Approximately 250 participants are expected to be enrolled into this research study.

The study aims to see if chimeric antigen receptor T cells (CAR T) cells made from healthy donors are an effective treatment to prevent relapse in participants who have lymphoma DNA detected in their blood by an investigational test. For reference, CAR T cells are T cells (a type of immune system white blood cell) that have been engineered to attack cancer cells, like lymphoma.

The study evaluates two investigational products – ALLO-647, an antibody (protein) that may help prepare the body for receiving CAR T cells from healthy donors, and a CAR T cell treatment called cemacabtagene ansegedleucel or cema-cel.

In order to participate you must meet the following criteria:

• 1. Have large B-cell lymphoma per WHO 2017 histologically confirmed by pathology report.
  • Diffuse LBCL (DLBCL) not otherwise specified, EBV+ DLBCL, DLBCL with IRF4/MUM1 rearrangement
  • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
  • Primary mediastinal B-cell lymphoma
• Have completed a full course of standard 1L therapy (e.g., R-CHOP, dose-adjusted EPOCH-R, Pola-R-CHP) as intended. 1L therapy must have included an anthracycline and an anti-CD20 monoclonal antibody. If radiation therapy has been planned as part of 1L therapy, radiation must also have been completed. Participants cannot have received additional lines of therapy.
• Per the Lugano criteria 2014, participant achieved complete response (CR), or partial response (PR) suitable for observation at the end of 1L therapy based on PET/CT evaluation between 3 and 8 weeks after last treatment (e.g., dose of chemotherapy, fraction of radiation).
• Have an MRD blood sample collected between 3 and 8 weeks after last 1L treatment (e.g., dose of chemotherapy, fraction of radiation) and MRD test is positive.
• Are an adult ≥18 years of age.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Have adequate hematological function without transfusion or growth factor support in last 7 days, including:
  • Absolute neutrophil count (ANC) ≥1,000/μL
  • Platelet count ≥50,000/μL
  • Hemoglobin ≥8 g/dL (≥5 mmol/L)
  • Absolute lymphocyte count (ALC) ≥300/μL
• Have adequate renal function: estimated creatinine clearance ≥50 mL/min (Cockcroft-Gault) or directly measured with 24-hour urine collection.
• Have adequate liver function, including: 
  • Total bilirubin ≤1.5 × upper limit of normal (ULN), except in patients with Gilbert’s Syndrome who must have a total bilirubin ≤3 × ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
  • Alkaline phosphatase ≤2.5 × ULN
• Have normal blood oxygen saturation level (SpO2) >92% on room air.
• Have left ventricular ejection fraction (LVEF) ≥40%.
• Non-hematologic toxicities related to prior therapy must be recovered to baseline or grade ≤1 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 unless the toxicities are clinically insignificant (e.g., alopecia, fatigue, peripheral neuropathy with adequate performance status).
• For female participants: negative serum pregnancy test at screening except for those who are of non-childbearing potential.
• Non-childbearing potential must meet at least 1 of the following criteria:
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological, physiological or medicinal cause; status may be confirmed with a serum follicle stimulating hormone level confirming the postmenopausal state.
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy.
  • Have a medically confirmed ovarian failure.
• All other female participants (including female participants with tubal ligations) are considered to be of childbearing potential.
• Fertile male participants and female participants of childbearing potential must be willing to use a highly effective method of contraception for at least 12 months (6 months for males) after last study treatment.
• Have evidence of a signed and dated informed consent document indicating that the participant has been informed of all aspects of the study.
• In the opinion of the investigator, are willing and able to comply with scheduled visits, treatment or observation plan, laboratory tests, and other procedures.

You will be excluded from the study if any of the following criteria apply to you:

• Hvve large B-cell lymphoma (LBCL) includes history of central nervous system (CNS) involvement (primary or secondary) or has arisen or transformed from other malignancy (e.g., transformed follicular lymphoma or marginal zone lymphoma, Richter’s transformation). Additionally, T-cell/histiocyte rich LBCL is excluded.
• Have a history of clinically significant CNS dysfunction, e.g., seizure disorder, cerebrovascular ischemia or hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement.
• Have had prior irradiation to >25% of the bone marrow.
• Have had prior treatment with anti-CD19 targeted therapies.
• Have concurrent participation in an interventional clinical study after minimal residual disease (MRD) testing is performed (long-term follow-up after completion of treatment is acceptable).
• Have had anti-cancer treatment including radiation after MRD testing is performed.
• Have ongoing treatment with systemic immunosuppressive agents within 2 weeks prior to enrollment, with the exception of physiologic replacement corticosteroids at <10 mg of prednisone equivalents daily, inhaled steroid for asthma, topical steroid use, or another local corticosteroid administration.
• Have active and clinically significant autoimmune disease requiring systemic therapy within the last 2 years including, but not limited to, Guillain-Barre syndrome, rheumatoid arthritis, and systemic lupus erythematosus. Participants with a history of autoimmune-related hypothyroidism on a stable dose of replacement hormone and participants with well-controlled type 1 diabetes on a stable insulin regimen may be eligible.
• Are known to be refractory to platelet or red blood cell transfusions.
• Have active systemic bacterial, fungal, or viral infections requiring systemic treatment (e.g., HIV). Additionally viral infections which may not be requiring systemic treatment during screening as described: 
  • Participants who are seropositive for cytomegalovirus (CMV) are excluded unless polymerase chain reaction (PCR) confirms negative for viral load and participant can receive required study prophylaxis.
  • Participants who are seropositive for hepatitis C are excluded unless participant has received a definitive course of direct-acting antiviral agents and PCR confirms negative viral status.
  • Participants who are seropositive for current or previous hepatitis B infection (Positive for Hep B surface Ag or Hep B core antibody) are excluded.
• Have any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
• Have a history myocardial infarction or unstable angina within 6 months prior to screening. Any unstable arrhythmia or clinically significant and active pericardial effusion is also excluded.
• Have a history of hypertensive crisis within 6 months prior to enrollment.
• Have a history of solid organ or hematopoietic stem cell transplant (corneal transplant permitted).
• Have a history of hemophagocytic lymphohistiocytosis (HLH).
• Have a history of progressive multifocal leukoencephalopathy (PML).
• Have a history of clinically significant liver disease, including non-viral hepatitis or cirrhosis within the past 12 months.
• Have a history of clinically significant pulmonary disease, such as severe chronic obstructive pulmonary disease (COPD), bronchospasm requiring intubation, interstitial lung disease, or pneumonitis (drug-related or autoimmune). Active clinically significant pleural effusion is also excluded.
• Have known or suspected hypersensitivity to murine and bovine products.
• Have a history of another primary malignancy or bone marrow disorder (e.g., myelofibrosis, smoldering multiple myeloma) within 3 years prior to enrollment (with the exception of carcinoma in situ of the breast, bladder, or cervix, localized prostate cancer (Gleason score ≤6) in observation, and adequately treated non-melanoma skin cancer.
• Have other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation in the judgment of the investigator.
• Are unwilling to undergo an extended safety monitoring period (up to 15 years after cema-cel infusion).
• Are pregnant or breastfeeding or planning to become pregnant or breastfeed during the study or within 12 months (6 months for males) of enrollment.
• Have received live vaccine(s) within 28 days prior to enrollment.

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.