Phase 1 N=13 Treatment

T-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma

Myeloma-Multiple · Myeloma, Plasma-Cell

Bottom Line

View on ClinicalTrials.gov: NCT03958656 ↗

Enrolled (actual)

Serious AEs

30.0%

Results posted

Sep 2021

Primary outcome: Primary: Number of Participants That Had Any Grade ≤2, and 3, 4 and 5 Adverse Events Following Administration of T Cells Expressing Anti- Signaling Lymphocytic Activation Molecule F7 (SLAMF7) Chimeric Antigen Receptor (CAR) — 0; 0; 1; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Cyclophosphamide (Drug); Fludarabine (Drug); Rimiducid (Drug); Anti-Signaling lymphocytic activation molecule F7 (SLAMF7) chimeric antigen receptor (CAR) T cells (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Oct 2020

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants That Had Any Grade ≤2, and 3, 4 and 5 Adverse Events Following Administration of T Cells Expressing Anti- Signaling Lymphocytic Activation Molecule F7 (SLAMF7) Chimeric Antigen Receptor (CAR)	0; 0; 1; 0; 3; 3	—

Summary

Background: Multiple myeloma is a blood cancer that is usually incurable. T cells are part of the immune system. Researchers think changing a person's T cells to recognize their cancer could help the person's body kill tumor cells. This is a new approach that uses a patient's own cells to target multiple myeloma. Objective: To see if giving anti-Signaling lymphocytic activation molecule F7 (SLAM7) chimeric antigen receptor (CAR) T cells with a stop switch to people with multiple myeloma is safe and to see if adding a gene to stop T-cell activity can limit toxicity of this therapy. Eligibility: People ages 18-73 with multiple myeloma for which prior standard treatment has not worked Design: Participants will be screened with: * Medical history * Physical exam * Blood, urine, and heart tests * Bone marrow samples: A needle inserted into the participant's bone will remove marrow. * Imaging scans: Participants will lie in a machine that takes pictures of the body. Participants will have apheresis. They will receive a catheter or central line: A plastic tube will be inserted into a chest or arm vein. Blood will be removed and the T cells separated. The rest of the blood will be returned to the participant. The T cells will be manipulated in the lab. Participants will get chemotherapy through the central line for 3 days. Participants will receive the manipulated T cells through the central line. They will stay in the hospital at least 9 days. Participants will have follow-up visits 2 weeks then 1, 2, 3, 4, 6, 9, and 12 months after the infusion. They will then have visits every 6 months for 3 years. Then they will be contacted once per year for 15 years. All visits will include blood tests, and 3 visits will include bone marrow biopsies....

Eligibility Criteria

INCLUSION CRITERIA - MULTIPLE MYELOMA:
Signaling lymphocytic activation molecule F7 (SLAMF7) expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry. A specific quantitative level of SLAMF7 expression for eligibility is not specified, but patients with multiple myeloma cells that are negative for SLAMF7 by flow cytometry and immunohistochemistry will not be enrolled. These assays must be performed at the National Institutes of Health (NIH). It is not required that the specimen used for SLAMF7 determination comes from a sample that was obtained after the patient's most recent treatment. If paraffin embedded unstained samples of bone marrow involved with MM or a plasmacytoma are available, these can be shipped to the NIH for SLAMF7 staining, otherwise new biopsies will need to be performed for determination of SLAMF7 expression.
SLAMF7 expression will need to be documented on the majority of malignant plasma cells by flow cytometry at the NIH at some time after the original chimeric antigen receptor (CAR)-SLAMF7 T-cell infusion in all patients undergoing a second CAR-SLAMF7 T-cell infusion on this clinical trial.
Bone marrow plasma cells must make up less than or equal to 50% of total bone marrow cells based on a bone marrow biopsy performed within 24 days of the start of protocol treatment.
Patients must have received at least 3 different prior treatment regimens for multiple myeloma (MM)
Must have prior exposure to an immunomodulatory drug (IMiD) such as lenalidomide and a proteasome inhibitor
Patients must have measurable MM as defined by at least one of the criteria below.
Serum M-protein greater or equal to 0.6 g/dL.
Urine M-protein greater or equal to 200 mg/24 h.
Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
A biopsy-proven plasmacytoma at least 1.5 cm in largest dimension
Bone marrow core biopsy with 30% or more plasma cells

INCLUSION CRITERIA - OTHER:

Greater than or equal to 18 years of age and less than or equal to age 73.
Able to understand and sign the Informed Consent Document.
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2
Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and for four months after last day of receiving protocol treatment.
Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
A patient with a negative blood polymerase chain reaction (PCR) test for hepatitis B deoxyribonucleic (DNA) test can be enrolled. If hepatitis B DNA (PCR) testing is not available, patients with a negative hepatitis B surface antigen and negative hepatitis B core antibody can be enrolled.
Patients must be tested for the presence of Hepatitis C antigen by PCR and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative in order to be eligible. Only if Hepatitis C PCR testing is not available in a timely manner, patients who are Hepatitis C antibody-negative can be enrolled.
Absolute neutrophil count greater than or equal to 1000/mm^3 without the support of filgrastim or other growth factors within the previous 10 days.
Platelet count greater than or equal to 55,000/mm^3 without transfusion support in the past 14 days.
Hemoglobin greater than or equal to 8.0 g/dL.
Less than 5% plasma cells in the peripheral blood leukocytes
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of the institutional normal.
Serum creatinine less than or equal to 1.5 mg/dL.
Total bilirubin less than or equal

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Data sourced from ClinicalTrials.gov (NCT03958656). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.