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

NCT ID: NCT04864522

Last Updated: 2023-11-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-31
• Study Completion Date: 2023-11-30

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SLAMF7 FPBMC

Intervention Type: DRUG

Participants will receive 8 weekly infusions of SLAMF7 FPBMC, then 8 additional infusions every 2 weeks.

Interventions

SLAMF7 FPBMC

Participants will receive 8 weekly infusions of SLAMF7 FPBMC, then 8 additional infusions every 2 weeks.

Intervention Type: DRUG

Other Intervention Names

CS-1 FPBMC

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Laahn Foster

Associate Progessor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laahn Foster, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

Ashley Donihee

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

HSR200107

Identifier Type: -

Identifier Source: org_study_id