Overview
Phase I/II Trial of Cord Blood-Derived NK Cells Genetically Engineered With NY-ESO-1 TCR/IL-15 Cell Receptor for Relapsed/Refractory Multiple Myeloma
Status:
Recruiting
Recruiting
Trial end date:
2028-08-31
2028-08-31
Target enrollment:
0
0
Participant gender:
All
All
Summary
To find the recommended dose of NY-ESO-1 TCR/IL-15 NK cells that can be given to patients with relapsed or refractory MM. To learn if the dose of NY-ESO-1 TCR/IL-15 NK cells found in Part A can help to control the disease.Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
M.D. Anderson Cancer CenterTreatments:
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Criteria
Inclusion criteria:1. Patients with multiple myeloma with an expression of NY-ESO-1 by immunohistochemistry
in the pre-enrollment tumor sample
2. Patients are HLA-A*02:01positive on HLA typing
3. Patients with relapsed or refractory MM (patients with solitary plasmacytoma are not
eligible) who meet the following criteria:
1. > or = 4 prior lines of therapy (including exposure to at least one proteasome
inhibitor, ImiD, and anti-cd38 antibody and bcma targeted agent
2. have measurable disease (serum monoclonal (M) protein level ≥0.5 g/dL, and/or
urine M protein level ≥200 mg/day, and/or involved serum FLC level ≥10 mg/dL
provided the serum-free light-chain ratio is abnormal *refractory is defined as a
documented progressive disease during or within 60 days [measured from the last
dose of any drug within the regimen] of completing treatment with the last
anti-myeloma regimen before study entry.
4. Patients with relapsed or refractory plasma cell leukemia who have received at least
two previous regimens
5. Patients at least 2 weeks from the last anti-myeloma therapy at the time of starting
lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or
other targeted therapies until at least three days prior to administration of
lymphodepleting chemotherapy. Small molecule targeted therapies will not include
targeted immune therapies, such as daratumumab, isatuximab or elotuzumab.
6. Prior autologous/allogeneic transplants are allowed.
7. Prior cell therapy is allowed against targets other than NY-ESO-1.
8. Patients must have recovered from systemic toxicity of prior anti-myeloma therapy at
the start of lymphodepletion.
9. No active or uncontrolled infection at the start of lymphodepletion and/or cell
infusion.
10. No therapeutic systemic corticosteroids (>/= 20 mg prednisone or equivalent) within 72
hours of lymphodepleting therapy.
11. Patients with concurrent autoimmune diseases with neurologic involvement, such as
multiple sclerosis will be excluded.
12. Localized radiotherapy to one or more disease sites is allowed prior the infusion
provided that there are additional disease sites that are not irradiated
13. Karnofsky Performance Scale > 50%.
14. Adequate organ function:
1. Renal: Serum creatinine = 1.5 mg/dL or estimated Glomerular Filtration Rate
(eGFR using the CKI-EPI equation) >/= 45 ml/min/1.73 m2.
2. Hepatic: ALT/AST = 2.5 x ULN or = 5 x ULN if documented liver metastases,
Total bilirubin = 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom
total bilirubin must be = 3.0 mg/dL. No history of liver cirrhosis. No ascites.
3. Cardiac: Cardiac ejection fraction >/= 50%, no clinically significant pericardial
effusion as determined by an ECHO or MUGA, and no uncontrolled arrhythmias or
symptomatic cardiac disease.
4. Pulmonary: No clinically significant pleural effusion (per PI discretion),
baseline oxygen saturation > 92% on room air.
15. Able to provide written informed consent.
16. 18-80 years of age.
17. Weight ≥40 kg
18. All participants who are able to have children must practice effective birth control
while on study and up to 3 months post completion of study therapy. Acceptable forms
of birth control for female patients include: hormonal birth control, intrauterine
device, diaphragm with spermicide, condom with spermicide, or abstinence, for the
length of the study. If the participant is a female and becomes pregnant or suspects
pregnancy, she must immediately notify her doctor. If the participant becomes pregnant
during this study, she will be taken off this study. Men who are able to have children
must use effective birth control while on the study. If the male participant fathers a
child or suspects that he has fathered a child while on the study, he must immediately
notify his doctor.
19. Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional
responsibilities to various regulatory agencies.
20. Participants must not have received any live vaccines within 30 days prior to
enrollment.
21. No active infection requiring systemic antibiotics
22. Adequate bone marrow function without the need for transfusion in the last 7 days as
described below, unless the pancytopenia is due to marrow replacement by myeloma:
- Absolute neutrophil count (ANC) ≥1000 /µL
- Hemoglobin ≥8 g/dL
- Platelet count ≥50,000 /µL
23. No bridging anti-myeloma therapy within 14 days of lymphodepleting therapy
Criteria for Cell Infusion-
Patients who meet one of the following criteria on the day of infusion will have their
administration delayed for 24 hours. If these problems persist beyond 24 hours, patients
will not receive their cell infusion.
1. cardiac arrhythmias not controlled with medical management
2. hypotension requiring vasopressor support
3. suspected or active uncontrolled infection
Exclusion Criteria:
1. None