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Recurrent Plasma Cell MyelomaPhase 1NCT03710421

CS1-CAR T Therapy Following Chemotherapy in Treating Patients With Relapsed or Refractory CS1 Positive Multiple Myeloma

A Phase 1 study testing CS1-CAR T Therapy, Cyclophosphamide and Fludarabine in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by City of Hope Medical Center at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of CS1-chimeric antigen receptor (CAR) T therapy after chemotherapy in treating patients who have CS1 positive multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CS1-CAR T Therapy, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
23 Apr 2019to 13 Aug 2027
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative.
  • Assent, when appropriate, will be obtained per institutional guidelines.
  • Karnofsky Performance Status (KPS) of >= 70%.
  • Life expectancy >= 16 weeks.
  • Participant must have a confirmed diagnosis of active MM as defined by the International Myeloma Working Group (IMWG) criteria.
  • Participant must have a confirmed CS1+ MM as evaluated by City of Hope (COH) Pathology Core.
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  • Participant must have measurable disease defined as meeting at least one of the criteria below:
  • Serum M-protein >= 0.5 g/dL.
  • Urine M-protein >= 200 mg/24 hour.
  • Involved serum free light chain (sFLC) level >= 10 mg/dL with abnormal kappa/lambda ratio.
  • Measurable biopsy-proven plasmacytomas (>= 1 lesion that has a single diameter >= 2 cm)
  • Bone marrow plasma cells >= 30%.
  • Participant must have relapsed or refractory disease after all 3 prior treatment regimens with the following requirements:
  • Participant must have received prior treatment with an immunomodulatory agent.
  • Participant must have received prior treatment with a proteasome inhibitor.
  • Participant must have received prior treatment with an anti-CD38 antibody.
  • Participants must be refractory to last line of therapy prior to study enrollment (refractory myeloma is defined as disease that is nonresponsive, progression on treatment, or shows progression within 60 days after the last prior line of therapy).
  • Participants who were not candidates to receive one or more of the above treatments are eligible; however, the reason must be clearly documented in the case report form.
  • Note: induction chemotherapy, autologous stem-cell transplantation (ASCT), and maintenance therapy should be considered as 1 "regimen."
  • Additionally, if a participation underwent autologous transplant he/she be >= 90 days from transplant at the time of enrollment.
  • Total serum bilirubin =< 2.0 mg/dL.
  • Participants with Gilbert syndrome may be included if their total bilirubin is =< 3.0.
  • Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) < 2.5 x ULN.
  • Serum creatinine =< 2.5 x ULN or estimated creatinine clearance of >= 40 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis.
  • Absolute neutrophil count >= 1000/uL. Transfusions and growth factors must not be used to meet these requirements at initial screening.
  • Hemoglobin (Hb) >= 8 g/dl. Transfusions and growth factors must not be used to meet these requirements at initial screening.
  • Platelet count >= 50,000/uL (>= 30,000/uL if bone marrow plasma cells are >= 50% of cellularity). Transfusions and growth factors must not be used to meet these requirements at initial screening.
  • Left ventricular ejection fraction >= 45% within 8 weeks before enrollment.
  • Oxygen (O2) saturation >= 92%.
  • Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test.
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy.
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).

Who cannot join

  • Prior allogeneic stem cell transplantation.
  • Autologous transplantation =< 90 days of enrollment.
  • Growth factors within 14 days of enrollment.
  • Platelet transfusions within 7 days of enrollment.
  • Epstein-Barr virus (EBV) positivity by polymerase chain reaction (PCR) at the time of enrollment
  • Participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
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  • Participants with known additional malignancy that is progressing or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  • Participants with toxicities from prior therapies, with the exception of peripheral neuropathy attributable to bortezomib, that have not recovered to grade =< 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria or to the subject's prior baseline.
  • Participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) positive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections.
  • Participants with active auto-immune disease, including connective tissue disease, sarcoidosis, multiple sclerosis, inflammatory bowel disease or have a history of severe (as judged by the principal investigator) autoimmune disease that will require prolonged immunosuppressive therapy.
  • Have New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of recent (within 6 months) myocardial infarction.
  • Participants with a history or presence of clinically relevant central nervous system (CNS) pathology such as uncontrolled seizure disorder, stroke, severe brain injuries, dementia, cerebellar disease or psychosis.
  • Participants with known active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
  • Participants with plasma cell leukemia (PCL) or symptomatic amyloidosis. However, participants with a prior history of PCL are not excluded.
  • Participants with any known contraindications to leukapheresis, cyclophosphamide, fludarabine, cetuximab or tocilizumab.
  • Dependence on corticosteroids.
  • Defined as doses of corticosteroids of greater than or equal to 10 mg/day of prednisone or equivalent doses of other corticosteroids.
  • Note: Topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed.
  • Participants with inadequate venous access for leukapheresis, and who are either unable to or unwilling to have a supportive line (temporary or other) placed for the procedure.
  • Females only: Pregnant or breastfeeding.
  • Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
  • Prospective subjects who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase I Study to Evaluate Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CS1-Targeting, Hinge-Optimized, 41BB-Costimulatory Chimeric Antigen Receptor and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients With CS1+ Multiple Myeloma

This phase I trial studies the side effects and best dose of CS1-chimeric antigen receptor (CAR) T therapy after chemotherapy in treating patients who have CS1 positive multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Immune cells can be engineered to kill multiple myeloma cells by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells using a lentiviral vector such as CS1, that allows them to recognize multiple myeloma cells. These engineered immune cells, CS1-CAR T cells, may kill multiple myeloma cells.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and tolerability of intravenous (i.v.) delivered autologous CS1-CAR T cells for research participants with CS1+ recurrent/refractory multiple myeloma (MM).

SECONDARY OBJECTIVES:

  1. Evaluate the response rates at days 28, 100, and 180 post CAR T cell infusion.

II. Measure the persistence of CS1-CAR T cells in blood and marrow. III. Measure phenotype and anti-tumor functionality of CS1-CAR T cells in marrow and blood.

IV. Measure the levels of cytokines in blood and marrow, and soluble CS-1 in blood post infusion as a surrogate indicator of CAR T cell activity.

  1. Evaluate CS-1 expression on MM cancer cells before, during and at progressive disease (PD) to determine antigenic loss.

EXPLORATORY OBJECTIVE:

  1. Describe the percentage of MM cells that express CS-1 surface marker before, during and at PD.

OUTLINE: This is a dose-escalation study of CS1-CAR T cells.

Patients undergo leukapheresis over 2-4 hours. Beginning 3-4 weeks, patients receive cyclophosphamide intravenously (IV) on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients then undergo CS1-CAR T therapy over 10-15 minutes on day 0.

After completion of study treatment, patients are followed up at 1 day, at least every 2 days for up to a minimum of 14 days, weekly for 1 month, monthly for 1 year, then periodically for up to 15 years.

Being tested
CS1-CAR T Therapy, Cyclophosphamide, Fludarabine, Leukapheresis
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CS1-CAR T TherapyProcedure or surgery

    Also called CS1-CAR T Infusion, CS1-CAR T-cell Therapy

    Undergo CS1-CAR T therapy

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

Study groups in NCT03710421
Study groupRoleWhat they receive
Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)ExperimentalPatients undergo leukapheresis over 2-4 hours. Beginning 3-4 weeks, patients receive cyclophosphamide IV on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients then undergo CS1-CAR T therapy over 10-15 minutes on day 0.
Receives: Procedure: CS1-CAR T Therapy; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicity (DLT) and all other toxicities

    Tables will be created to summarize all toxicities and side effects by organ, severity (Common Terminology Criteria for Adverse Events version 5.0), and attribution. Rates and associated 90% confidence limits will be estimated for participants experiencing DLTs.

    Measured: Up to 12 months

  2. Incidence of all other toxicities

    Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Will include cytokine release syndrome (CRS) based on the revised CRS grading system, and heart failure based on New York Heart Association criteria.

    Measured: Up to 15 years

  3. Opportunistic infections

    Measured: Up to 15 years

  4. Prolonged lymphopenia (lasting more than 12 weeks)

    Measured: Up to 15 years

Secondary outcomes (7)

  1. Disease response

    Disease status will be evaluated based on the International Myeloma Working Group for Multiple Myeloma. Descriptive statistics will be provided for patient demographics, phenotype and functionality of modified T cells as well as anti-tumor immune response.

    Measured: Up to 180 days

  2. Expansion/persistence of chimeric antigen receptor (CAR) T cells

    Rates and associated 90% confidence limits will be estimated for participants achieving persistence/expansion of T cells at 28 days. To further study T cell expansion and persistence, area under the curve of log10 copies/ug of genomic deoxyribonucelic acid over the 28 day period post T cell infusion will be calculated for each participant and presented both graphically and using descriptive statistics.

    Measured: At 28 days post CAR T cell infusion

  3. Phenotype and anti-tumor functionality of modified T cells in marrow and blood

    Descriptive statistics will be provided for patient demographics, phenotype and functionality of modified T cells as well as anti-tumor immune response.

    Measured: Up to 15 years

  4. Cytokine and soluble CS-1 levels in blood and marrow

    Statistical and graphical methods will be used to describe the cytokine levels (marrow and blood) over the study period.

    Measured: Up to 15 years

  5. Disease free survival (DFS)

    Rates and associated 90% confidence limits will be estimated for participants experiencing DFS. Kaplan Meier methods will be used to describe the survival distributions both statistically and graphically.

    Measured: At 12 months

  6. Progression-free survival

    Kaplan Meier methods will be used to describe the survival distributions both statistically and graphically.

    Measured: At 12 months

  7. CS1 expression on multiple myeloma cells

    Measured: Baseline up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2018
  2. Study start23 Apr 2019
  3. Primary completion13 Aug 2027 (estimated)
  4. Study completion13 Aug 2027 (estimated)

Why it stopped: Slow/Low Accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03710421
Sponsor's protocol ID
17403
Other IDs
NCI-2018-02022, 17403
Status last verified
Oct 2026
First submitted
5 Oct 2018
Last updated
30 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CS1-CAR T Therapy, Cyclophosphamide and Fludarabine in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicity (DLT) and all other toxicities (time frame: Up to 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03710421.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.

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