| Eligibility |
Inclusion Criteria:
1. Ability to provide informed consent and documentation of informed consent prior to
initiation of any study-related tests or procedures that are not part of
standard-of-care for the patient's disease. Patients must also be willing and able to
comply with study procedures, including the acquisition of specified research
specimens
2. Age = 18 years old & life expectancy > 3 months
3. Expression of HLA-A*0201 as determined by high resolution sequence-based typing method
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with exception
of ECOG > 1 if related to recent bone fracture
5. Patients must have confirmed diagnosis of MM
6. Have identified relapsed/refractory disease which includes:
1. Previous therapy consisting of at least three (3) standard regimens, including a
proteasome inhibitor, IMiD, or anti-CD38 targeting therapy.
Note: Induction therapy, autologous stem cell transplantation (ASCT) &
maintenance therapy if given sequentially without intervening progressive disease
(PD) are considered one 'regimen'
2. Refractory MM may be defined as disease that is refractory to treatment while on
therapy or that shows progression within 60 days of the last therapy.
7. Have measurable disease as defined by:
1. Serum M protein = 0.5 g/dL
2. Urine M protein = 200 mg/24hr
3. Serum free light chains (FLC) = 10 mg/dL with abnormal FLC ratio Note: Patients
with IgA MM in whom serum protein electrophoresis (sPEP) is deemed unreliable,
due to co-migration of normal serum proteins with the paraprotein in the ß
region, may be considered eligible as long as total serum IgA level is > normal
range.
8. Acceptable laboratory parameters as follows:
1. AST/ALT = 2.5 × ULN
2. Total bilirubin = 1.5 × ULN, except patients with Gilbert's syndrome, who may
enroll if the conjugated bilirubin is within normal limits
3. Serum creatinine = 2.5 mg/dL or estimated creatinine clearance (CL) = 30 mL/min &
not dialysis-dependent
4. ALC > 1000 cells/µL
9. Recovery to Grade 1 or baseline of non-hematologic toxicities from prior treatments,
excluding alopecia & Grade 2 peripheral neuropathy
10. Female patients of childbearing potential must test negative for pregnancy at
enrollment and during the study. Sexually active women of child-bearing potential,
unless surgically sterile, must be willing to use a highly effective method of birth
control defined as those which result in a low failure rate (i.e., less than 1% per
year) such as implants, injectables, combined oral contraceptives, intra-uterine
devices (IUDs) or vasectomized partner
11. Male patients with partners of childbearing potential must be either vasectomized or
agree to use a condom in addition to having their partners use another method of
contraception resulting in a highly effective method of birth control defined as those
which result in a low failure rate (i.e., less than 1% per year) such as implants,
injectables, combined oral contraceptives, or IUDs. Patients should not have sexual
intercourse with females who are either pregnant or lactating without double-barrier
contraception • Is not pregnant or breastfeeding, or expecting to conceive or father
children within the projected duration of the trial, starting with the prescreening or
screening visit through one year from administration of NEXI-002 T cells
Exclusion Criteria:
1. Have active cerebral or meningeal disease related to the underlying malignancy
2. Have hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS
syndrome, amyloidosis, plasmacytoma, significant autoimmune or other malignant disease
3. History of allogeneic hematopoietic stem cell transplantation
4. Have active or uncontrolled infections with positive cultures and/or requiring
treatment with IV anti-infective agents
5. Echocardiogram or MUGA with left ventricular ejection fraction < 45%
6. History of clinically significant cardiovascular disease including but not limited to:
1. Myocardial infarction or unstable angina within the 6 months prior to the
initiation of study
2. Stroke or transient ischemic attack within 6 months prior to initiation of study
3. Clinically significant cardiac arrhythmia
4. Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mmHg, diastolic
blood pressure (DBP) > 100 mmHg
5. Congestive heart failure (New York Heart Association [NYHA] class III-IV)
6. Pericarditis or clinically significant pericardial effusion
7. Myocarditis
7. Clinically significant pulmonary compromise, including a requirement for supplemental
oxygen use to maintain adequate oxygenation
8. Eligible patients will not be on any steroids =10 mg per day prednisone or equivalent
or other immunosuppressants such as tacrolimus, cyclosporine, etc.
a. Intermittent topical, inhaled or intranasal corticosteroids are allowed
9. History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring
systemic anticoagulation within 6 months before enrollment
10. History of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus
erythematosus, etc.) resulting in end organ injury or requiring systemic
immunosuppression / systemic disease modifying agents within the last 2 year prior to
enrollment. Subjects with a history of autoimmune-related hypothyroidism on a stable
dose of thyroid replacement hormone and subjects with controlled Type 1 diabetes
mellitus on a stable insulin regimen may be eligible for the study
11. Human immunodeficiency virus (HIV) seropositive; HIV testing within 2 years of
enrollment
12. Seropositive for and with evidence of active viral infection with hepatitis B virus
(HBV). Patients who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA
negative are eligible
1. Patients who had HBV but have received an antiviral treatment and show
non-detectable viral DNA for 6 months are eligible
2. Patients who are seropositive because of HBV vaccine are eligible
13. Seropositive for and with active viral infection with hepatitis C virus (HCV)
a. Patients who had HCV but have received an antiviral treatment and show no
detectable HCV viral DNA for 6 months are eligible
14. Second primary invasive malignancy that has not been in remission for more than 2
years. Exceptions that do not require a 2-year remission include: non-melanoma skin
cancer; carcinoma in situ (cervix, bladder, breast, etc.) or squamous intraepithelial
lesion on Pap smear; localized prostate cancer (Gleason score < 6); or resected
melanoma in situ
15. History of trauma or major surgery within 4 weeks prior to the initiation of study
16. Any serious underlying medical or psychiatric condition that would impair the ability
of the patient to receive or tolerate the planned treatment and follow up
17. Known hypersensitivity to any component of NEXI-002 T cells, cyclophosphamide,
fludarabine or tocilizumab
18. Vaccination with any live virus vaccine within 6 weeks prior to the initiation of
study treatment. Inactivated annual influenza vaccination is allowed
19. Dementia or altered mental status that would preclude understanding and rendering of
informed consent
20. History of seizures, aphasia, psychosis or other chronic clinically significant
neurologic disorders
a. Patients with remote history of seizures that are well controlled on anti-seizure
medications and without any seizure episode for 6 months are eligible
21. Any issue that in the opinion of the investigator, would contraindicate the patient's
participation in the study or confound the results of the study
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