A Study to Assess CART19 for B Cell Malignancies

Overview

About this study

The purpose of this study is to find out more about the side effects of the CAR-T therapy called IC19/1563 and what dose of IC19/1563 is safe for patients.

The therapy, IC19/1563, uses some of the patients own immune cells, called T cells, to kill cancer. T cells fight infections and, in some cases, can also kill cancer cells. In this study, some of the patient's T cells will be removed from their blood. In the laboratory, we will put a new gene into the T cells. This gene allows the T cells to recognize and possibly treat the cancer. The new modified T cells are called the IC19/1563 treatment. The dose of IC19/1563 will depend on when the patient is enrolled on to the study.

 

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 - Registration:

  • Age ≥ 18 years.
  • Relapsed or refractory CD19+ B cell malignancies of the one of the following histopathology:
    • Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease defined as:
      • Two or more prior lines of therapy, at least one anthracycline containing regimen, unless intolerable. Exception: Patients with Richter transformation of CLL are eligible if they had ≥one prior treatment, including prior BTK inhibition;
      • Demonstration of progressive or stable disease by PET/CT or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma;
      • Measurable disease defined as measurable by CT portion of a PET/CT: To be considered measurable, the must be at least one lesion that has a single diameter of (>1.5 cm Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
  • Biopsy proven SLL or flow cytometry proven CLL; relapsed disease defined as:
    • ≥ two prior lines of therapy, including prior BTK inhibition;and/or ≥6 months of second line prior BTK inhibition (e.g. venetoclax and ibrutinib). Exception: Patients in SD or PR with a known ibrutinib resistance mutation (BTK or phospholipase Cγ2) may be included even if on ibrutinib therapy for less than 6 months
    • Demonstration of progressive or stable disease by PET/CT or CT criteria according to the iwCLL2018 criteria;
    • Measurable disease by CT portion of a PET/CT where at least one lesion has a single diameter of > 1.5 cm or peripheral blood ALC of > 5000.
      • Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
  • ECOG Performance Status (PS) 0 or 1 (Appendix I).
  • The following laboratory values obtained ≤ 14 days prior to registration:
    • Hemoglobin ≥ 8.0 g/dL;
    • Absolute neutrophil count (ANC) ≥ 500/mm^3;
    • Platelet count ≥ 30,000/mm^3;
    • Total bilirubin ≤ 2.0 mg/dL (with the exception of subjects with Gilbert’s syndrome. Subjects with Gilbert’s syndrome may be included if their Total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN);
    • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN;
    • PT/INR and/or aPTT ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (for patients receiving anticoagulation, there should be no prior history of bleeding, and no recent DVT/PE within the last 6 months of enrollment);
    • Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula below:
      • Cockcroft-Gault Equation:
      • Creatinine clearance for males =     (140 - age)(weight in kg)
      •                                                           (72)(serum creatinine in mg/dL)
      • Creatinine clearance for females =  (140 - age)(weight in kg)(0.85)
      •                                                            (72)(serum creatinine in mg/dL)
  • Cardiac ejection fraction ≥ 50% and no evidence of clinically significant pericardial effusion as determined by an ECHO or MUGA scan.
  • Baseline oxygen saturation > 92% on room air
  • Negative serum pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
  • Women patients of child bearing potential, including women with tubal ligations, must commit to using use 2 highly effective  forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives) for the duration of the study and for 12 months following IC19/1563 therapy.
  • Provide written informed consent.
  • Willingness to provide mandatory blood specimens for correlative research.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

Registration - Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant persons;
    • Nursing persons;
    • Women of childbearing potential who are unwilling to employ highly effective contraception.
  • Sexually active males who are not willing to use contraception during the study and for ≥ 12 months after IC19/1563 therapy.
  • Patients who are able to obtain market approved CD19 CAR T-cell therapies.
  • Live vaccine ≤ 6 weeks prior to start of registration.
  • Autologous stem cell transplant ≤ 6 weeks of registration.
  • History of allogenic stem cell transplant if was performed less than 100 days prior to registration, if patients have active GVHD or are if patients are on chronic immunosuppression. Patients with allogeneic transplantation more than 100 days prior to registration, with no active GVHD and who are not on immunosuppression are eligible.
  • History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
  • Any form of primary immunodeficiency such as Severe Combined Immunodeficiency Disease.
  • Current need of systemic corticosteroid therapy, in doses over 20 mg /day of prednisone or equivalent forms of steroids.
  • History of severe immediate hypersensitivity reaction to CART19, stem cell infusion DMSO or any of the CAR-T cryopreservation ingredients
  • History of malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, breast), unless disease free for ≥ 2 years
  • Clinically significant active infection (e.g., simple UTI, bacterial pharyngitis allowed) or currently receiving IV antibiotics or have received IV antibiotics ≤ 7 days prior to registration. Note: prophylactic antibiotics, antivirals and antifungals are permitted.
  • Known history of HIV infection or acute or chronic hepatitis B or hepatitis C infection. Subjects with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines. Prophylactic antiviral therapy should be considered per institutional guidelines.
  • History of any of the following cardiovascular conditions ≤ 6 months:
    • Class III or IV heart failure as defined by the New York Heart Association (NYHA);
    • cardiac angioplasty or stenting;
    • myocardial infarction;
    • unstable angina; or
    • other clinically significant cardiac disease.
  • Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or that, in the judgment of the investigator, would make the subject inappropriate for entry into the study.
  • Receiving any other investigational agent which would be considered as a treatment for the primary disease.

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

Rochester, Minn.

Mayo Clinic principal investigator

Saad Kenderian, M.B., Ch.B.

Contact us for the latest status

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-20512716

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