| Eligibility |
Inclusion Criteria:
- Male or female patients aged 18 years or older.
- Participants must have histologically confirmed, CD19 positive relapsed or refractory
NHL that meets at least one of the following treatment indications.
- Relapsed after 2 or more lines of chemotherapy, or:
- Refractory to chemotherapy, defined as:
• Progressive disease while receiving last chemotherapy, or Persistent disease
after first line chemotherapy treatment with curative intent or stable disease
lasting =6 months after last chemotherapy, or relapse within 6 months of last
chemotherapy, or disease progression or elapse =12 months after prior autologous
stem cell transplant, or:
- Relapsed disease that is ineligible to receive hematopoietic stem cell
transplantation due to comorbidities or age or patient preference
- Subjects must have a CD3% = 15% of total PBMCs (monocytes + lymphocytes).
- ECOG Performance status = 2
- At least one measurable lesion according to Lugano Revised Response Criteria for
Malignant Lymphoma.
- Minimum of 2 weeks since prior radiation therapy or systemic therapy to treat
malignancy at the time of leukapheresis.
- Total bilirubin = 1.5X institutional upper limit of normal.
- AST (SGOT)/ALT (SGPT) = 2.5 X institutional upper limit of normal.
- Calculated creatinine clearance = 30mL/min estimated by the Cockcroft - Gault formula.
- Cardiac ejection fraction of =45%, and no more than trivial (or trace, minimal or
mild)pericardial effusion, as determined by an echocardiogram.
- Adequate pulmonary function, defined as = Grade 1 dyspnea (unless considered secondary
to lymphoma) and oxygen saturation (SaO2) = 92% on room air. If pulmonary function
tests (PFTs) are performed based on the clinical judgment of the treating physician,
patients with forced expiratory volume in 1 second (FEV1) = 50% of predicted and
diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) of = 40% of
predicted will be eligible.
- Subjects (or legal guardians) must have the ability to understand and the willingness
to sign a written informed consent document.
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use a contraceptive method with a failure rate of < 1%
per year during the treatment period and for at least 90 days after the UF-KURE19
CAR-T cell infusion. A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not undergone
surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive
methods with a failure rate of < 1% per year include bilateral tubal ligation, male
sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing
intrauterine devices, and copper intrauterine devices. The reliability of sexual
abstinence should be evaluated in relation to the duration of the clinical trial and
the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm, as defined: With
female partners of childbearing potential, men must remain abstinent or use a condom
plus an additional contraceptive method that together result in a failure rate of < 1%
per year during the treatment period and for at least 6 months after the UF-KURE19
CAR-T cell infusion. Men must refrain from donating sperm during this same period.
With pregnant female partners, men must remain abstinent or use a condom during the
treatment period and for at least 6 months after the UF-KURE19 CAR-T cell infusion to
avoid potential embryonal or fetal exposure. The reliability of sexual abstinence
should be evaluated in relation to the duration of the clinical trial and the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception.
Exclusion Criteria:
- Autologous stem cell transplant within 6 weeks of informed consent
- History of allogeneic hematopoietic stem cell transplantation.
- Active central nervous system or leptomeningeal involvement by lymphoma. Subjects with
untreated brain metastases/CNS disease will be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.
Patients with a history of CNS or meningeal involvement must be in a documented
remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days
prior to registration.
- Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ
(e.g. cervix, bladder, breast).
- Less than 28 days elapsed between prior treatment with investigational agent(s) and
leukapheresis.
- New York Heart Association class III-IV congestive heart failure.
- Cardiovascular disorders including unstable angina pectoris, clinically significant
cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic
attack, or other ischemic event) within 6 months prior to registration.
- Known human immunodeficiency virus infection or acquired immunodeficiency syndrome
related illness.
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell
therapy may be associated with the potential for teratogenic or abortifacient effects.
Women of childbearing potential must have a negative serum pregnancy test. Because
there is an unknown, but potential risk for adverse events in nursing infants
secondary to treatment of the mother with CAR-T cells, breastfeeding should be
discontinued. These potential risks may also apply to other agents used in this study.
- Evidence of myelodysplastic syndrome or cytogenetic abnormality indicative of
myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
- Serologic status reflecting active hepatitis B or C infection. Patients that are
positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or
hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to
enrollment. (PCR positive patients will be excluded).
- Patients with history of clinically relevant CNS pathology such as epilepsy, seizure
disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain
injuries, dementia and Parkinson's disease.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations
that would limit compliance with study requirements.
- History of active autoimmune disease (i.e. rheumatoid arthritis, systemic lupus
erythematosus) with requirement of systemic immunosuppressive medications other than
low dose steroids [i.e. maximum of 15mg prednisone equivalent] within the last 6
months.
- Circulating malignant B cells in peripheral blood detected by complete blood count at
the time of subject enrollment.
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