Clinical trial NCT04864522: Phase I/II Study of SLAMF7 FPBMC/CS-1 FPBMC in Relapsed/Refractory Multiple Myeloma
Official title: Phase I/II Study of Anti-CD3 x Anti-SLAMF7 (Anti-CS-1) Bispecific Antibody Armed Fresh Peripheral Blood Mononuclear Cells (SLAMF7 FPBMC) in Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Relapsed
Refractory
Fresh Peripheral Blood Mononuclear Cells (FPBMC)
Bispecific antibodies
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2021-04-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: SLAMF7 FPBMC
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicities (DLTs)
timeFrame: From time of informed consent through one week following 8th FPBMC infusion
measure: Adverse event profile
timeFrame: From time of informed consent through 30 days following last FPBMC infusion
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: About once a month during study treatment (for about 6 months), then about every 3 months for 3 years or until first progression
measure: Minimal Residual Disease (MRD) status
timeFrame: Through first progression of disease (maximum of 3 years from first infusion)
measure: Overall Survival (OS)
timeFrame: Through 3 years after first FPBMC infusion
measure: Cellular anti-myeloma responses
timeFrame: Multiple timepoints through 12 months after last FPBMC infusion
measure: Progression-free survival (PFS)
timeFrame: From informed consent through first progression or 3 years after enrollment
measure: Humoral anti-myeloma responses
timeFrame: Multiple timepoints through 12 months after last FPBMC infusion
measure: Lymphocyte response following infusions of SLAMF7 FPBMC
timeFrame: Blood samples collected prior to first infusion and then before the second through fifth infusions
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: Ashley Donihee
state: Virginia
Study officials:
affiliation: University of Virginia
name: Laahn Foster, MD
role: PRINCIPAL_INVESTIGATOR
References: