Multiple Myeloma
Conditions
Keywords
Multiple myeloma, Relapsed, Refractory, Fresh Peripheral Blood Mononuclear Cells (FPBMC), Bispecific antibodies
Brief summary
The purpose of this study is to understand the safety and estimate the efficacy of combining anti-CD3 x anti-SLAMF7 bispecific antibody fresh peripheral blood mononuclear cells (SLAMF7 FPBMC/CS1 FPBMC) for patients with relapsed and/or refractory multiple myeloma. Patients receive 8 weekly doses and then 8 more doses every 2 weeks of SLAMF7 FPBMC by intravenous infusion.
Detailed description
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure. The white blood cells, specifically T cells, are then mixed with two proteins, OKT3 and IL-2, which activate the cells to multiply. The activated T cells are coated with the OKT3 and elotuzumab (an anti-SLAMF7 drug) to produce bispecific fresh peripheral blood mononuclear cells (FPBMC). About 72 hours after the leukapheresis procedure, SLAMF7 FPBMC infusions will start. After about 8-9 weeks, participants will have another leukapheresis procedure and then receive doses every 2 weeks for 8 more doses. Before, throughout and following SLAMF7 FPBMC, research blood will be collected to better understand immune response. Disease status will be checked regularly during and after study treatment.
Interventions
DRUGSLAMF7 FPBMC
Participants will receive 8 weekly infusions of SLAMF7 FPBMC, then 8 additional infusions every 2 weeks.
Sponsors
University of Virginia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
SLAMF7 FPBMC
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must have received ≥ 2 consecutive cycles of treatment which include an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody either used individually or in combination 2. Documented refractory or relapsed myeloma * Refractory is defined as progression while on treatment or within 60 days of last treatment 3. Measurable disease based on at least one of the following lab results within 28 days of enrollment * Serum IgG, IgA, or IgM M-protein ≥ 1.0 g/dL * Urine M-protein ≥ 200 mg excreted in a 24-hr collection sample * Involved serum free light chain (FLC) ≥ 100 mg/L provided the FLC ratio is abnormal 4. ECOG Performance Status 0 -2 5. Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or Echocardiogram) 6. Age ≥ 18 years at the time of consent (Written informed consent and HIPAA authorization for release of personal health information) 7. Females of childbearing potential, and males, must be willing to use an effective method of contraception for the duration of the treatment with study drug plus 90 days (duration of sperm turnover). 8. Adequate cardiac function as defined as: * No EKG evidence of acute ischemia * No EKG evidence of clinically significant conduction system abnormalities in the opinion of the treating investigator * No EKG evidence of \> Grade 2 (\> 480 ms) QTc prolongation * No uncontrolled angina or severe ventricular arrhythmias * No clinically significant pericardial disease * No history of myocardial infarction (MI) in the last 6 months * No Class 3 or higher New York Heart Association Congestive Heart Failure 9. Demonstrate adequate organ function as defined below; all screening labs should be performed within 14 days prior to enrollment. * Absolute lymphocyte count ≥ 400/mm3 * Absolute neutrophil count ≥ 1,000/mm3 * Platelets ≥ 75,000/mm3 * Calculated Creatinine Clearance ≥ 30 ml/min * Serum total bilirubin ≤ 1.5 x upper limit of normal * AST and ALT \< 2.5 times normal
Exclusion criteria
1. Known hypersensitivity to elotuzumab (Elo) 2. Amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome, or known central nervous system (CNS) involvement 3. Receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment. * NOTE: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 4. Active autoimmune disease that has required systemic treatment in the past 2 years before enrollment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 5. Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment 6. Active liver disease (such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis) 7. HIV positive or known active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected) or Hepatitis B (e.g. HBsAg reactive) virus 8. Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed) 9. Has an active infection requiring systemic therapy 10. History of active TB (Bacillus Tuberculosis) 11. Has received a live vaccine within 30 days of enrollment. 12. Anti-myeloma drug therapy (including radiation therapy) ≤ 14 days prior to apheresis 13. History of myocardial infarction (within 6 months of enrollment), stable or unstable angina 14. History of another malignancy within the past 3 years before enrollment. -- Exceptions include: * Basal cell carcinoma of the skin or squamous cell carcinoma of the skin, * In situ cancers that have undergone potentially curative therapy 15. Prisoners or patients who are incarcerated 16. Patients who are compulsorily detained for treatment of either a psychiatric or physical illness 17. Pregnant or breastfeeding females: Females of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities (DLTs) | From time of informed consent through one week following 8th FPBMC infusion | An adverse event that is considered at least possibly related to SLAMF7 FPBMC and meets at least one of the protocol-defined criteria |
| Adverse event profile | From time of informed consent through 30 days following last FPBMC infusion | Severity, frequency, category, seriousness and duration of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Through 3 years after first FPBMC infusion | Duration of time from consent through death or 3 years after first FPBMC infusion |
| Cellular anti-myeloma responses | Multiple timepoints through 12 months after last FPBMC infusion | IFN-gamma Elispots stimulated by a multiple myeloma cell line |
| Overall response rate (ORR) | About once a month during study treatment (for about 6 months), then about every 3 months for 3 years or until first progression | As defined by International Myeloma Working Group (IMWG) response criteria (partial response (PR), very good partial response (VGPR), complete response (CR), stringent CR (sCR) |
| Humoral anti-myeloma responses | Multiple timepoints through 12 months after last FPBMC infusion | Anti-SOX2 IgG antibodies in the serum by specific ELISA |
| Lymphocyte response following infusions of SLAMF7 FPBMC | Blood samples collected prior to first infusion and then before the second through fifth infusions | T cell count and count for T cell subpopulations |
| Progression-free survival (PFS) | From informed consent through first progression or 3 years after enrollment | Duration of time from consent through first progression (or end of follow-up) |
| Minimal Residual Disease (MRD) status | Through first progression of disease (maximum of 3 years from first infusion) | Assessed by ClonoSeq, only for patients who achieve stringent CR or CR |
Countries
United States
Outcome results
None listed