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

NCT03710421 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 17403NCI-2018-02022
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (4)

• 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.

  Up to 12 months

• 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.

  Up to 15 years

• Opportunistic infections

  Up to 15 years

• Prolonged lymphopenia (lasting more than 12 weeks)

  Up to 15 years

Secondary Outcomes (7)

• Disease response

  Up to 180 days

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

  At 28 days post CAR T cell infusion

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

  Up to 15 years

• Cytokine and soluble CS-1 levels in blood and marrow

  Up to 15 years

• Disease free survival (DFS)

  At 12 months

Other Outcomes (1)

• MM cells that are CS-1 positive

  Up to 15 years

Study Arms (1)

Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)

EXPERIMENTAL

Patients 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.

Procedure: CS1-CAR T Therapy; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis

Interventions

CS1-CAR T Therapy PROCEDURE

Undergo CS1-CAR T therapy

Also known as: CS1-CAR T Infusion, CS1-CAR T-cell Therapy

Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine; Leukapheresis

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Myo Htut

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 18, 2018
• Study Start: April 23, 2019
• Primary Completion (Estimated): February 23, 2027
• Study Completion (Estimated): February 23, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)