CART-BCMA Cells for Multiple Myeloma

NCT02546167 | Completed Phase 1 DMC

• 1 other identifier: UPCC 14415, 822756
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label, single-center, pilot study to assess the safety and feasibility of infusion of autologous T cells expressing BCMA (B-cell maturation antigen)-specific chimeric antigen receptors with tandem TCR and 4-1BB costimulatory domains (referred to as CART-BCMA ) in adult patients with multiple myeloma (MM). CART-BCMA cells will be given as a split dose intravenous infusion over 3 days. The duration of active intervention and monitoring is approximately 2 years.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  Study related adverse events (defined as ≥ Grade 3 signs/symptoms according to CTCAE 4.03, laboratory toxicities, and clinical events) that are "possibly", "probably", or "definitely" related to study treatment any time from the first day of study treatment until end of study visit.

  2 years

Study Arms (3)

Cohort 1

EXPERIMENTAL

will receive 1-5x10\^7 CART-BCMA cells given as a split dose infusion over 3 days.

Biological: CART-BCMA

Cohort 2

EXPERIMENTAL

Cyclophosphamide infusion prior to 1-5x10\^7 CART BCMA cells given as a split dose infusion over 3 days.

Biological: CART-BCMA

Cohort 3

EXPERIMENTAL

Cyclophosphamide infusion prior to 1-5x10\^8 CART BCMA cells given as a split dose infusion over 3 days.

Biological: CART-BCMA

Interventions

CART-BCMA BIOLOGICAL

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

You may qualify if:

• Subjects must have a confirmed prior diagnosis of active MM as defined by the updated IMWG criteria101..
• Subjects must have relapsed or refractory disease after either one of the following:
• At least 3 prior regimens, which must have contained an alkylating agent, proteasome inhibitor, and immunomodulatory agent (IMiD).
• At least 2 prior regimens if "double-refractory" to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents.
• Note: Induction therapy, stem cell transplant, and maintenance therapy, if given sequentially without intervening progression, should be considered as 1 "regimen".
• Subjects must have signed written, informed consent.
• Subjects must be ≥ 18 years of age.
• Subjects must be at least 90 days since autologous or allogeneic stem cell transplant, if performed.
• Subjects must have adequate vital organ function:
• Serum creatinine ≤ 2.5 or estimated creatinine clearance ≥30 ml/min and not dialysis-dependent.
• Absolute neutrophil count ≥1000/μl and platelet count ≥50,000/μl (≥30,000/μl if bone marrow plasma cells are ≥50% of cellularity).
• SGOT ≤ 3x the upper limit of normal and total bilirubin ≤ 2.0 mg/dl (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome).
• Left ventricular ejection fraction (LVEF) ≥ 45%. LVEF assessment must have been performed within 8 weeks of enrollment.
• Toxicities from prior therapies, with the exception of peripheral neuropathy attributable to bortezomib, must have recovered to grade ≤ 2 according to the CTC 4.0 criteria or to the subject's prior baseline.
• Subjects must have an ECOG performance status of 0-2.

You may not qualify if:

• Be pregnant or lactating.
• Have inadequate venous access for or contraindications to leukapheresis.
• Have any active and uncontrolled infection.
• Have active hepatitis B, hepatitis C, or HIV infection.
• Any uncontrolled medical or psychiatric disorder that would preclude participation as outlined.
• Have NYHA Class III or IV heart failure, unstable angina, or a history of recent (within 6 months) myocardial infarction or sustained (\>30 seconds) ventricular tachyarrhythmias.
• Have received prior gene therapy or gene-modified cellular immunotherapy. Subject may have received, however, non-gene-modified autologous T-cells in association with an anti-myeloma vaccine (e.g., hTERT or MAGEA3) or vaccination against infectious agents (e.g., influenza or pneumococcus) as was performed on our previous studies.
• Have active auto-immune disease, including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease, or multiple sclerosis, or have a history of severe (as judged by the principal investigator) autoimmune disease requiring prolonged immunosuppressive therapy.
• Have a history of neurodegenerative or central nervous system movement disorder.
• Have prior or active central nervous system (CNS) involvement (e.g. leptomeningeal disease, parenchymal masses) with myeloma. Screening for this (e.g. with lumbar puncture) is not required unless suspicious symptoms or radiographic findings are present. Subjects with calvarial disease that extends intracranially and involves the dura will be excluded, even if CSF is negative for myeloma.
• Have active acute or chronic graft-versus-host-disease (GVHD), or require immunosuppressant medications for GVHD, within 4 weeks of enrollment.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, Vogl DT, Weiss BM, Dengel K, Nelson A, Plesa G, Chen F, Davis MM, Hwang WT, Young RM, Brogdon JL, Isaacs R, Pruteanu-Malinici I, Siegel DL, Levine BL, June CH, Milone MC. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019 Mar 21;129(6):2210-2221. doi: 10.1172/JCI126397.

  PMID: 30896447 DERIVED

• Bu DX, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG, Bennett P, Barton N, Wu Q, Zhang J, Wang Y, Wei L, Cogan S, Ezell T, Joshi S, Latimer KJ, Granda B, Tschantz WR, Young RM, Huet HA, Richardson CJ, Milone MC. Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget. 2018 May 25;9(40):25764-25780. doi: 10.18632/oncotarget.25359. eCollection 2018 May 25.

  PMID: 29899820 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Adam Cohen, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 9, 2015
• First Posted: September 10, 2015
• Study Start: September 3, 2015
• Primary Completion: August 21, 2019
• Study Completion: July 27, 2020
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

US (1)