The purpose of this study is to understand the safety and estimate the efficacy of combining
anti-CD3 x anti-SLAMF7 bispecific antibody armed activated T cells (SLAMF7 BATs/CS1 BATs) for
patients with relapsed and/or refractory multiple myeloma. Patients receive 4 weekly doses
and then 4 more doses every 2 weeks of SLAMF7 BATs by intravenous infusion. If patients have
at least stable disease after these infusions, then they may receive additional infusions
every 4 weeks up to a maximum of 21 infusions (including the initial 8 infusions).
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via
leukapheresis procedure at approximately 3 to 4 weeks prior to the first SLAMF7 BATs
infusion. The white blood cells, specifically T cells, are then mixed with two proteins, OKT3
and IL-2, which activate the cells to multiply.
After approximately 14 days in culture, the activated T cells are coated with the OKT3 and
elotuzumab (an anti-SLAMF7 drug) to produce bispecific antibody armed T cells (BATs). Cells
are then frozen and stored until scheduled to be infused.
About 4 weeks after the leukapheresis procedure, SLAMF7 BATs infusions will start. At week 10
of SLAMF7 BATs infusions, disease status will be checked and patients who have stable disease
or better may be eligible for additional SLAMF7 BATs infusions about every 4 weeks. Before,
throughout and following SLAMF7 BATs, research blood will be collected to better understand
immune response. Disease status will be checked regularly during and after study treatment.
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) ≥ 55% 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. Eligible for apheresis
9. 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
10. 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.
