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

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ClinicalTrials.gov Identifier: NCT04864522
Recruitment Status : Not yet recruiting
First Posted : April 29, 2021
Last Update Posted : April 29, 2021
Sponsor:
Information provided by (Responsible Party):
Laahn Foster, University of Virginia

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 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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: SLAMF7 BATs Early Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: SLAMF7 BATs
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Anti-CD3 x Anti-SLAMF7 (Anti-CS-1) Bispecific Antibody Armed Activated T-Cells (SLAMF7 BATs/CS-1 BATs) in Relapsed/Refractory Multiple Myeloma
Estimated Study Start Date : May 15, 2021
Estimated Primary Completion Date : January 1, 2026
Estimated Study Completion Date : January 1, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
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.
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).
Other Name: CS-1 BATs




Primary Outcome Measures :
  1. Unacceptable adverse events (UAEs) [ Time Frame: From time of informed consent through 30 days following last BATs infusion ]
    An adverse event that is considered at least possibly related to SLAMF7 BATs and meets at least one of the protocol-defined criteria

  2. Progression-free survival (PFS) [ Time Frame: From informed consent through first progression or 1 year after enrollment ]
    Duration of time from consent through first progression (or end of follow-up)


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: About 4 weeks following 8th BATs infusion ]
    As defined by International Myeloma Working Group (IMWG) response criteria (partial response (PR), very good partial response (VGPR), complete response (CR), stringent CR (sCR)

  2. Adverse event profile [ Time Frame: From time of informed consent through 30 days following last BATs infusion ]
    Severity, frequency, category, seriousness and duration of adverse events

  3. Minimal Residual Disease (MRD) status [ Time Frame: About 4 weeks following 8th BATs infusion ]
    Assessed by ClonoSeq, only for patients who achieve stringent CR

  4. Overall Survival (OS) [ Time Frame: Through 12 months after last BATs infusion ]
    Duration of time from consent through death or 12 months after last BATs infusion

  5. Number of IFNgamma secreting cells [ Time Frame: Multiple timepoints through 12 months after last BATs infusion ]
    As measured by Elispots



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04864522


Contacts
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Contact: Ioannis Vassalos, MD 434-924-9496 iv4wn@virginia.edu
Contact: Jungeun Kim, PhD 434-982-3365 jk9te@hscmail.mcc.virginia.edu

Locations
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United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
Contact: Ioannis Vassalos, MD    434-924-9496    iv4wn@virginia.edu   
Contact: Jungeun Kim, PhD    434-982-3365    jk9te@hscmail.mcc.virginia.edu   
Principal Investigator: Laahn Foster, MD         
Sponsors and Collaborators
University of Virginia
Investigators
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Principal Investigator: Laahn Foster, MD University of Virginia
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Responsible Party: Laahn Foster, Assistant Progessor, University of Virginia
ClinicalTrials.gov Identifier: NCT04864522    
Other Study ID Numbers: HSR200107
First Posted: April 29, 2021    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Laahn Foster, University of Virginia:
Multiple myeloma
Relapsed
Refractory
BATs
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases