IRB Study Number 24-831
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective:
To assess the efficacy of cema-cel vs. observation in participants with MRD+ LBCL
Secondary Objectives:
• To further characterize the efficacy of cema-cel vs. observation in participants with MRD+ LBCL
• To assess the overall safety profile of cema-cel and ALLO-647
Inclusion Criteria
- Large B-cell lymphoma per WHO 2017 histologically confirmed by pathology report.
a. Diffuse LBCL (DLBCL) not otherwise specified, EBV+ DLBCL, DLBCL with IRF4/MUM1 rearrangement,
b. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,
c. Primary mediastinal B-cell lymphoma.
Participant has 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 (Cheson 2014), participant achieved CR, or 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).
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.
Adult participants ≥18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Adequate hematological function without transfusion or growth factor support in last 7 days, including:
a. Absolute neutrophil count (ANC) ≥1,000/μL
b. Platelet count ≥50,000/μL
c. Hemoglobin ≥8 g/dL (≥5 mmol/L)
d. Absolute lymphocyte count (ALC) ≥300/μL
Adequate renal function: estimated creatinine clearance ≥50 mL/min (Cockcroft-Gault) or directly measured with 24-hour urine collection.
Adequate liver function, including:
a. Total bilirubin ≤1.5 × ULN, except in patients with Gilbert’s Syndrome who must have a total bilirubin ≤3 × ULN,
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN,
c. Alkaline phosphatase ≤2.5 × ULN.
Normal blood oxygen saturation level (SpO2) >92% on room air.
Left ventricular ejection fraction (LVEF) ≥40%.
Non-hematologic toxicities related to prior therapy must be recovered to baseline or grade ≤1 per 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:
a. 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.
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy.
c. 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 as outlined in Section 4.5.2 for at least 12 months (6 months for males) after last study treatment.
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, is willing and able to comply with scheduled visits, treatment or observation plan, laboratory tests, and other procedures.
Exclusion Criteria
LBCL includes history of 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.
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.
Prior irradiation to >25% of the bone marrow.
Prior treatment with anti-CD19 targeted therapies.
Concurrent participation in an interventional clinical study after MRD testing is performed (long-term follow-up after completion of treatment is acceptable).
Anti-cancer treatment including radiation after MRD testing is performed.
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.
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.
Participants known to be refractory to platelet or red blood cell transfusions.
Participants with 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:
a. Participants who are seropositive for CMV are excluded unless PCR confirms negative for viral load and participant can receive required study prophylaxis.
b. 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.
c. Participants who are seropositive for current or previous hepatitis B infection (Positive for Hep B surface Ag or Hep B core antibody) are excluded.
Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
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.
History of hypertensive crisis within 6 months prior to enrollment.
History of solid organ or hematopoietic stem cell transplant (corneal transplant permitted).
History of hemophagocytic lymphohistiocytosis (HLH).
History of progressive multifocal leukoencephalopathy (PML).
History of clinically significant liver disease, including non-viral hepatitis or cirrhosis within the past 12 months.
History of clinically significant pulmonary disease, such as severe COPD, bronchospasm requiring intubation, interstitial lung disease, or pneumonitis (drug-related or autoimmune). Active clinically significant pleural effusion is also excluded.
Known or suspected hypersensitivity to murine and bovine products.
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.
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.
Participants unwilling to undergo an extended safety monitoring period (up to 15 years after cema-cel infusion).
Pregnant or breastfeeding or planning to become pregnant or breastfeed during the study or within 12 months (6 months for males) of enrollment.
Live vaccine(s) received within 28 days prior to enrollment.
