Phase I/II Study of SLAMF7 FPBMC/CS-1 FPBMC in Relapsed/Refractory Multiple Myeloma (MM FPBMC)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: SLAMF7 FPBMC

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Ashley Donihee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SLAMF7 FPBMC; Participants will undergo apheresis to collect cells to make SLAMF7 fresh peripheral blood mononuclear cells (FPBMC). These cells will be activated in the lab to fight against multiple myeloma. About 3-4 days after apheresis, participants will start receiving infusions of SLAMF7 FPBMC. Throughout treatment, participants will have blood taken for labs, to check disease status and also to look at immune response. Study treatment will stop if the participant has disease progression.

Drug: SLAMF7 FPBMC; Participants will receive 8 weekly infusions of SLAMF7 FPBMC, then 8 additional infusions every 2 weeks.; Other Names: CS-1 FPBMC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities (DLTs)	An adverse event that is considered at least possibly related to SLAMF7 FPBMC and meets at least one of the protocol-defined criteria	From time of informed consent through one week following 8th FPBMC infusion
Adverse event profile	Severity, frequency, category, seriousness and duration of adverse events	From time of informed consent through 30 days following last FPBMC infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	As defined by International Myeloma Working Group (IMWG) response criteria (partial response (PR), very good partial response (VGPR), complete response (CR), stringent CR (sCR)	About once a month during study treatment (for about 6 months), then about every 3 months for 3 years or until first progression
Minimal Residual Disease (MRD) status	Assessed by ClonoSeq, only for patients who achieve stringent CR or CR	Through first progression of disease (maximum of 3 years from first infusion)
Overall Survival (OS)	Duration of time from consent through death or 3 years after first FPBMC infusion	Through 3 years after first FPBMC infusion
Cellular anti-myeloma responses	IFN-gamma Elispots stimulated by a multiple myeloma cell line	Multiple timepoints through 12 months after last FPBMC infusion
Progression-free survival (PFS)	Duration of time from consent through first progression (or end of follow-up)	From informed consent through first progression or 3 years after enrollment
Humoral anti-myeloma responses	Anti-SOX2 IgG antibodies in the serum by specific ELISA	Multiple timepoints through 12 months after last FPBMC infusion
Lymphocyte response following infusions of SLAMF7 FPBMC	T cell count and count for T cell subpopulations	Blood samples collected prior to first infusion and then before the second through fifth infusions

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Laahn Foster, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): November 1, 2023
• Study Completion (Estimated): November 1, 2023

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Multiple myeloma; Relapsed; Refractory; Bispecific antibodies; Fresh Peripheral Blood Mononuclear Cells (FPBMC)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: HSR200107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No