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:

- 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 positron emission
tomography/computed tomography (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, and/or >= 6 months of second line prior BTK
inhibition (e.g. venetoclax and ibrutinib). Exception: Patients in stable
disease (SD) or partial response (PR) with a known ibrutinib resistance
mutation (BTK or phospholipase Cgamma2) 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 International Workshop on Chronic Lymphocytic Leukemia
(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 absolute blood lymphocyte
count (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

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

- Hemoglobin >= 8.0 g/dL (=< 14 days prior to registration)

- Absolute neutrophil count (ANC) >= 500/mm^3 (=< 14 days prior to registration)

- Platelet count >= 30,000/mm^3 (=< 14 days prior to registration)

- 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
upper limit of normal (ULN) and direct bilirubin =< 1.5 x ULN) (=< 14 days prior to
registration)

- Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 14 days
prior to registration)

- Prothrombin time (PT) / international normalized ratio (INR) and/or activated partial
thromboplastin time (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 deep
venous thrombosis/pulmonary embolism (DVT/PE) within the last 6 months of enrollment)
(=< 14 days prior to registration)

- Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (=< 14
days prior to registration)

- Cardiac ejection fraction >= 50% and no evidence of clinically significant pericardial
effusion as determined by an echocardiogram (ECHO) or multigated acquisition scan
(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)

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 graft-versus host disease (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 central nervous system (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
dimethyl sulfoxide (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 urinary tract infection [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 human immunodeficiency virus (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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/15/22. Questions regarding updates should be directed to the study team contact.

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.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
.
CLS-20512716

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