T-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma
A Phase I Clinical Trial of T-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma
2 other identifiers
interventional
13
1 country
1
Brief 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....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2019
CompletedFirst Posted
Study publicly available on registry
May 22, 2019
CompletedStudy Start
First participant enrolled
June 13, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 13, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 19, 2021
CompletedResults Posted
Study results publicly available
September 9, 2021
CompletedSeptember 9, 2021
August 1, 2021
1.3 years
May 21, 2019
June 22, 2021
August 19, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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)
Adverse Events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening or disabling, and Grade 5 is fatal.
Date treatment consent signed to date off study, approximately 3 months and 27 days for Level 1, 3 months and 18 days for Level 2, 5 months and 23 days for Level 3, and 1 month and 29 days for Level 4.
Other Outcomes (2)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Date treatment consent signed to date off study, approximately 3 months and 27 days for Level 1, 3 months and 18 days for Level 2, 5 months and 23 days for Level 3, and 1 month and 29 days for Level 4.
Number of Participants With a Response
At two and five weeks for stable disease and partial remission, respectively, and up to 5 months and 23 days for progressive disease
Study Arms (2)
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Dose Escalation
EXPERIMENTALPatients will receive escalating doses (up to 4 planned) of Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)-CAR+ T cells infused on day 0 + Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m\^22 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptor (CAR) T-cells Expansion Phase
EXPERIMENTALMaximum tolerated dose (MTD) dose of Anti-Anti-Signaling lymphocytic activation molecule F7 (SLAMF7)- CAR T Cells + Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Interventions
300 mg/m\^2 intravenous (IV) over 30 minutes on days -5, -4, and -3
30 mg/m\^2 intravenous (IV) over 30 minutes immediately following the cyclophosphamide on day -5, -4, and -3
0.4 mg/kg of Rimiducid intravenous (IV) over 2 hours. (A maximum of 2 doses separated by at least 48 hours) Note: Rimiducid may be administered as needed based on the patient condition at the discretion of the Principal Investigator.
0.3x10\^6- 12.0x10\^6 CAR+ T cells per kg of recipient bodyweight one-time dose on day 0
Eligibility Criteria
You may qualify if:
- 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
- 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.
- +15 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents.
- Patients on any anticoagulants except aspirin
- Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
- Patients that have active hemolytic anemia.
- Patients with second malignancies in addition to multiple myeloma are not eligible if the second malignancy has required treatment within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Women of child bearing potential cannot have a positive pregnancy test. Women of childbearing potential are defined as all women except women who are post-menopausal or who have had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least 1 year.
- Active systemic infections (defined as infections causing fevers or requiring anti-microbial treatment), active coagulation disorders or other major uncontrolled illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary, neurologic, psychiatric, or immune system, history of myocardial infarction, active cardiac arrhythmias, active obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid (prednisone, dexamethasone, etc.) is not allowed within 14 days prior to either the required leukapheresis or within 14 days prior to CAR Tcell infusion (and at any time after the CAR T-cell infusion unless approved by the Principal Investigator or an Associate Investigator).
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Patient unwilling to undergo intensive care unit treatment including mechanical ventilation, cardiopulmonary resuscitation, vasoactive drugs, and hemodialysis.
- History of allogeneic stem cell transplantation
- Patients with current spinal cord compression (without intradural myeloma involvement.
- Patients who have a history (or current evidence) of cerebrospinal fluid multiple myeloma, or intradural central nervous system masses.
- Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. James N. Kochendefer
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
James N Kochenderfer, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 21, 2019
First Posted
May 22, 2019
Study Start
June 13, 2019
Primary Completion
October 13, 2020
Study Completion
January 19, 2021
Last Updated
September 9, 2021
Results First Posted
September 9, 2021
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will not share