T Cells Expressing a Novel Fully-Human Anti-BCMA CAR for Treating Multiple Myeloma

NCT03602612 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 18012518-C-0125
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Multiple myeloma is a cancer of the blood plasma cells. It usually becomes resistant to standard treatments. Researchers have developed a procedure called gene therapy. It uses a person's own T cells, which are part of the immune system. The cells are changed in a lab and then returned to the person. Researchers hope the changed T cells will be better at recognizing and killing tumor cells. Objective: To test the safety of giving changed T cells to people with multiple myeloma. Eligibility: Adults ages 18-73 who have been diagnosed with multiple myeloma that has not been controlled with standard therapies. Design: Participants will be screened with: Medical history Physical exam Blood tests Heart function tests Bone marrow sample taken by needle in a hip bone. Scan of the chest, abdomen, and pelvis. They may have a brain scan. Pregnancy test Participants will have apheresis. Blood will be removed through an arm vein. The blood will be separated, and T cells removed. The rest of the blood will be returned through a vein in the other arm. Participants will have a central line placed in a large vein in the arm or chest. Participants will get 2 chemotherapy drugs by the central line over 3 days. Two days later, participants will get the changed T cells by the central line. They will stay in the hospital at least 9 days. Participants must stay near the hospital for 2 weeks. Participants will have 8 follow-up visits over the next year for blood and urine tests. They may have scans. Participants blood will be collected regularly over the next several years.

Conditions

Myeloma-Multiple; Myeloma, Plasma-Cell

Keywords

B-cell Maturation Antigen; Immunotherapy; Chimeric Antigen Receptors; Adoptive T Cell Therapy

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Anti-B Cell Maturation Antigen (BCMA) - Chimeric Antigen Receptor (CAR)-T Cells

  The MTD is the dose at which a maximum of 1 of 6 patients has a DLT. A DLT is Grade 3 toxicities possibly or probably or definitely related to the Anti-B cell maturation antigen (BCMA) - chimeric antigen receptor (CAR)-expressing T-Cells lasting more than 9 days. Grade 4 toxicities possibly or probably or definitely related to the anti-BCMA CAR T cells. Grade 3 is severe, and Grade 4 is life-threatening.

  First 28 days of treatment

• Number of Participants at Each Dose Level Who Experience a Dose-Limiting Toxicity (DLT)

  A DLT is Grade 3 toxicities possibly or probably or definitely related to the anti-B cell maturation antigen (BCMA) - chimeric antigen receptor (CAR)-T cells and lasting more than 9 days. Grade 4 toxicities possibly or probably or definitely related to the anti-BCMA CAR T cells. Grade 3 is severe, and Grade 4 is life-threatening.

  First 28 days of treatment

Other Outcomes (1)

• 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 16 months/17 days, 4 months/4 days, 4 months/18 days, 42 months/8 days, 20 months/19 days, 29 months/28 days, and 30 months/26 days for each Arm/Group respectively.

Study Arms (2)

1/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells dose escalation

EXPERIMENTAL

Patients will receive escalating doses (up to 5 planned) of 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\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Anti-B Cell Maturation Antigen (BCMA) chimeric antigen receptors (CARs) T cells

2/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells expansion phase

EXPERIMENTAL

6.0x10\^6 dose (maximum feasible dose) of CAR T Cells + Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 + Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Anti-B Cell Maturation Antigen (BCMA) chimeric antigen receptors (CARs) T cells

Interventions

Cyclophosphamide DRUG

300 mg/m\^2 intravenous (IV) over 30 minutes on days -5, -4, and -3

Also known as: Cytoxan

1/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells dose escalation; 2/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells expansion phase

Fludarabine DRUG

30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on day -5, -4, -3

Also known as: Fludara

1/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells dose escalation; 2/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells expansion phase

Anti-B Cell Maturation Antigen (BCMA) chimeric antigen receptors (CARs) T cells BIOLOGICAL

0.75x10\^6 - 12.0X10\^6 CAR+ T cells per kg of recipient bodyweight one time dose on day 0

1/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells dose escalation; 2/Conditioning chemotherapy plus chimeric antigen receptors (CARs) T-cells expansion phase

Eligibility Criteria

• Age: 18 Years - 73 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple Myeloma (MM) criteria:
• B Cell Maturation Antigen (BCMA) expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry. If patient has plasmacytomas, one plasmacytoma must be biopsied to demonstrate BCMA expression. A specific quantitative level of BCMA expression for eligibility is not specified, but patients with multiple myeloma cells that are negative for BCMA by flow cytometry and immunohistochemistry on either bone marrow biopsy or plasmacytoma biopsy 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 BCMA determination comes from a sample that was obtained after the patients 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 BCMA staining, otherwise new biopsies will need to be performed for determination of BCMA expression.
• BCMA 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 anti-BCMA chimeric antigen receptors (CARs) T-cell infusion in all patients undergoing a second anti-BCMA CAR T-cell infusion.
• Bone marrow plasma cells must make up less than 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
• Must have prior exposure to an immunomodulatory imide drugs ("IMiD") such as lenalidamide and a proteasome inhibitor
• Patients must have measurable MM as defined by at least one of the criteria below.
• One or more of these abnormalities defines measurable multiple myeloma:
• Serum M-protein greater or equal to 1.0 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 2.0 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.

You may not qualify if:

• 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 child-bearing 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 medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary, neurologic, or immune system, history of myocardial infarction, active cardiac arrhythmias including active atrial fibrillation history of any arrhythmias other than sinus tachycardia, or atrial fibrillation, currently taking any anti-arrythmic or congestive heart failure medications, 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 2 weeks prior to either the required leukapheresis or within 2 weeks prior to CAR T-cell infusion (and at any time after the CAR T cell infusion).
• 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 intra-dural central nervous system masse
• Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.
• Patients must not have required supplemental oxygen within the past month unless it was for a resolved infection.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Amatya C, Weissler KA, Lam N, Natrakul DA, Brudno JN, Cutmore LC, Mikkilineni L, Kochenderfer JN. Corticosteroids ameliorate CAR T-cell-induced cytokine-release syndrome without inhibiting multiple myeloma treatment. J Immunother Cancer. 2026 Feb 17;14(2):e012437. doi: 10.1136/jitc-2025-012437.

  PMID: 41702648 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; bis(3-bis(4-chlorophenyl)methyl-4-dimethylaminophenyl)amine; Receptors, Chimeric Antigen; Automobiles

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; Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear; Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Dr. James Kochenderfer
• Organization: National Cancer Institute

kochendj@mail.nih.gov

240-760-6062

Study Officials

• James N Kochenderfer, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

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: July 26, 2018
• First Posted: July 27, 2018
• Study Start: September 14, 2018
• Primary Completion: January 1, 2023
• Study Completion: April 21, 2026
• Last Updated: February 25, 2026
• Results First Posted: May 15, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)