A Study to Evaluate the Safety and Effectiveness of ALLO-501A CAR T Cell Therapy in Adults with Relapsed/ Refractory Large B Cell Lymphoma

Overview

About this study

The primary purpose of this study is to assess the safety and effectiveness of ALLO-501A to treat patients with relapsed/refractory large B cell lymphoma (LBCL) to determine the maximum tolerated dose (MTD).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017:
    • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL coexistent with follicular lymphoma of any grade, EBV+ DLBCL, T cell/histiocyte rich large B cell lymphoma, DLBCL with IRF4/MUM1 rearrangement;
    • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;
    • Transformation of follicular lymphoma or marginal zone lymphoma to DLBCL;
    • Primary mediastinal B cell lymphoma;
    • Follicular lymphoma Grade 3B;
    • For Phase 2: sufficient FFPE tumor samples must be available for histological and molecular subtype testing via a central lab along with a corresponding pathology report. A recent tumor sample obtained for the purpose of the study must be submitted however if not clinically feasible, an archival tumor biopsy from the most recent relapse may be submitted instead. Excisional biopsies should be submitted wherever possible; in cases where this is not possible, a core needle biopsy is allowable. Fine needle aspiration (FNA) is not allowed for this purpose.
  • At least 1 measurable lesion at time of enrollment according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2014):
    • A measurable node must have a longest transverse diameter greater than 1.5 cm;
    • A measurable extranodal lesion must have a longest diameter greater than 1.0 cm.
  • Relapsed or refractory disease after at least 2 lines of chemotherapy including an anthracycline and an anti-CD20 monoclonal antibody.
  • Male or female subjects age ≥18 years and < 80.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  • Absence of donor (product)-specific anti-HLA antibodies (DSA).
  • Adequate hematological function, including:
    • Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (without growth factor support the previous 7 days with filgrastim or 14 days with pegfilgrastim prior to screening);
    • Absolute lymphocyte count (ALC) ≥ 200/mm^3 or ≥ 0.2 × 10^9 /L;
    • Platelet count ≥ 50,000/mm^3 (without transfusion support during the previous 7 days prior to screening);
    • Hemoglobin ≥8 g/dL.
  • Adequate Renal Function, including:
    • Estimated creatinine clearance  ≥ 60 mL/min (Cockcroft-Gault) or directly measured with 24 hr urine collection.
  • Adequate Liver Function, including:
    • Total bilirubin ≤ 1.5 × ULN, except in subjects with Gilbert’s Syndrome who must have a total bilirubin ≤ 3 × ULN;
    • Aspartate and alanine aminotransferase (AST and ALT) ≤ 3 × ULN; ≤ 5.0 × ULN if there is liver involvement by the tumor; 
    • Alkaline phosphatase ≤ 2.5 × ULN (≤ 5 × ULN in case of bone metastasis).
  • Normal blood oxygen saturation levels (SpO2) > 92% on room air.
  • Left ventricular ejection fraction (LVEF) ≥ 50% and no pericardial or pleural effusion at screening.
  • Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤ 1 except for adverse events (AEs) not constituting a safety risk by investigator judgement.
  • Negative for hepatitis B antigen; positive hepatitis B tests can be further evaluated by confirmatory tests, and if viral load is negative, the subject can be enrolled.
  • Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by RT-PCR and subject must be HCV RNA negative.
  • Urine or serum pregnancy test (for females of childbearing potential) negative at screening.
  • Female subjects of 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 or physiological 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 subjects (including female subjects with tubal ligations) are considered to be of childbearing potential. Fertile male subjects and female subjects of childbearing potential must be willing to use a highly effective method of contraception for at least 12 months after cyclophosphamide.
    • Evidence of a signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
    • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Excusion Criteria:

  • Current or history of central nervous system (CNS) lymphoma.
  • Clinically significant CNS dysfunction; e.g., seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement.
  • Current thyroid disorder* (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy.
  • Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
  • Radiation therapy within 2 weeks prior to ALLO-647.
  • Prior irradiation to > 25% of the bone marrow.
  • Donor lymphocyte infusion (DLI) within 30 days prior to ALLO-647.
  • ASCT within last 6 weeks or allogeneic HSCT within last 3 months prior to ALLO647.
  • Prior treatment with anti-CD19 therapy, any gene therapy, any genetically modified cell therapy, or adoptive T cell therapy.
  • Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647. If the last immediate anti-cancer treatment contained an antibody-based agent(s) (approved or investigational), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) prior to receiving ALLO-647.
  • Participation in other studies involving investigational drug(s) within 28 days prior to ALLO-647 (with the exception of small molecule drugs for which only 14 days is required).
  • Prior treatment with anti-CD52 monoclonal antibody*.
  • Ongoing treatment with immunosuppressive agents:
    • Corticosteroid use within 1 week prior to first dose of lymphodepletion, with the exception of inhaled steroid for asthma, topical steroid use, or another local corticosteroid administration. Subjects requiring systemic steroids at daily doses > 10 mg prednisone (or corticosteroid equivalent), or those who are administered steroids for lymphoma control or WBC-count-lowering are not eligible to the study;
    • Infliximab must be stopped at least 45 days prior to administration of ALLO501A.
  • Active and clinically significant autoimmune disease requiring systemic therapy within the last 2 years including, but not limited to, Guillain-Barre syndrome, amyotrophic lateral sclerosis, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, immune cytopenias, severe psoriasis, autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
  • Subject known to be refractory to platelet or red blood cell transfusions.
  • Active acute or chronic graft versus host disease (GVHD), or GVHD requiring immunosuppressive treatment within 4 weeks of enrollment.
  • Subjects with active systemic bacterial, fungal, or viral infection requiring systemic treatment (including positive blood cultures within 7 days before enrollment).
  • Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted.
  • Any form of primary and acquired immunodeficiency (e.g., severe combined immunodeficiency disease).
  • Myocardial infarction or unstable angina within 6 months prior to screening.
  • Cardiac lymphoma involvement.
  • History of hypertension crisis or hypertensive encephalopathy within 6 months prior to screening.
  • Known or suspected hypersensitivity to murine and bovine products.
  • 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.
  • Subjects unwilling to undergo an extended safety monitoring period (long term follow up).

*Criteria specific to ALLO-647.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Javier Munoz, M.D., M.B.A.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20510895

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