Pilot Study of SLAMF7 BATs/CS-1 BATs in Relapsed/Refractory Multiple Myeloma

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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) ≥ 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04864522
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Virginia
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Laahn Foster, MD
Principal Investigator Affiliation University of Virginia
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

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.

Arms & Interventions

Arms

Experimental: SLAMF7 BATs

Participants will undergo apheresis to collect cells to make SLAMF7 BATs. These cells will be allowed to grow in the lab and a drug will be added to them to make them activated against multiple myeloma. About 4 weeks after apheresis, participants will start receiving SLAMF7 BATs. 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.

Interventions

Drug: - SLAMF7 BATs

Participants will receive 4 weekly infusions of SLAMF7 BATs, then 4 infusions every 2 weeks. Participants that have stable disease or better at week 10 of treatment may continue to receive an infusions every 4 weeks for up to a total of 21 infusions (including the first 8).

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Virginia, Charlottesville, Virginia

Status

Address

University of Virginia

Charlottesville, Virginia, 22903

Site Contact

Ioannis Vassalos, MD

iv4wn@virginia.edu

434-924-9496