Clinical Trial 23363

• Overview

  Study Title:

  A Randomized, Open-Label Study Evaluating the Efficacy and Safety of Cemacabtagene Ansegedleucel in Participants with Minimal Residual Disease after Response to First Line Therapy for Large B-Cell Lymphoma (Alpha3)

  Objective:

  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 Exploratory Objectives: -To characterize the relationship of ALLO-647 PK with host cell counts -To characterize the PK/PD of cema-cel -To evaluate immunogenicity of cema-cel and of ALLO-647 -To assess participant reported outcomes of study participants

• Treatments

  Therapies:

  Cell Therapy; Observational

  Medications:

  ALLO-647 (); Cema-cel (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Inclusion Criteria:
  • LBCL histologically confirmed, per WHO 2017, by pathology report with one of the listed histologies (a) AND with at least one of the listed clinical criteria (b): Histologies (one of the following): DLBCL not otherwise specified, EBV+ DLBCL, DLBCL with IRF4/MUM1 rearrangement, High-grade B-cell lymphoma not otherwise specified, or with MYC and BCL2 and/or BCL6 rearrangements, Primary mediastinal B-cell lymphoma. Clinical criteria (at least one of the following): International prognostic index (IPI) score of 2-5 at diagnosis, Ann Arbor Stage III or Stage IV disease at diagnosis, Ann Arbor Stage I or II disease at diagnosis with history of an equivocal response (eg, partial metabolic response) at interim or end of therapy PET/CT.
  • Participant has completed a full course of standard 1L therapy (eg, 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 after last treatment (eg, dose of chemotherapy, fraction of radiation) and remains in response on PET/CT within 5 weeks of randomization. Repeat PET/CT is not required if initial end of therapy PET/CT was performed within 5 weeks of randomization.
  • MRD blood sample was collected within 3 to 8 weeks (± 2 weeks) after last 1L treatment (eg, dose of chemotherapy, fraction of radiation) and MRD test performed as part of pre-screening was positive.
  • Adult participants 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Adequate hematological, cardiac and organ function as noted in protocol.
  • For female participants: negative serum pregnancy test at screening except for those who are of non-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.
  • Other criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • LBCL includes history of CNS involvement (primary or secondary) or has arisen or transformed from other malignancy . Additionally, T-cell/histiocyte rich LBCL is excluded.
  • History of clinically significant CNS dysfunction including seizure disorder uncontrolled in last 12 months, cerebrovascular ischemia or hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement.
  • Prior irradiation to greater than 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 or 5 half-lives (whichever is shorter) prior to enrollment, with the exception of physiologic replacement corticosteroids > Active and clinically significant autoimmune disease requiring systemic immunosuppressive therapy within the last 6 months 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 with a history of clinically significant and severe autoimmune disease must be discussed with the medical monitor.
  • Participants known to be refractory to platelet or red blood cell transfusions.
  • Participants with active systemic bacterial, fungal, or viral infections requiring systemic treatment (eg, 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 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 hepatitis B infection (positive for hepatitis B surface antigen (HBsAg) and/or positive for hepatitis B DNA via PCR reflex test) are excluded. Participants with a history of prior hepatitis B infection (ie, negative for HBsAg, positive for hepatitis B core antibody [HBcAb], and negative for hepatitis B DNA via PCR), who agree to an appropriate viral suppression therapy regimen may be eligible.
  • Any form of primary immunodeficiency.
  • History of 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
  • Additional criteria apply

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