Phase I Trial of BCMA-TGF-BETA CAR-T Cells in Relapsed, Refractory Myeloma

NCT05976555 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IIT-DHAKAL-TGF-BETA-BCMA
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase I, interventional, single-arm, open-label, dose-finding treatment study designed to evaluate the safety and efficacy of interleukin-7(IL-7) / interleukin-15 (IL-15) manufactured CAR T cells in adult patients with relapsed and/or refractory myeloma that have failed prior therapies.

Conditions

Multiple Myeloma

Keywords

CAR-T; Chimeric antigen receptor T-cell therapy; CAR Therapy

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events After BCMA-TGFβ CAR-T Cell Infusion

  Incidence of adverse events with grade 3 to 5 severity using NCI CTCAE version 5.0 and the Lee et al. consensus manuscript (which outlines the defining characteristics of each grade for cytokine release syndrome; please refer to the reference below).

  from infusion until Day +28 post CAR T infusion

Study Arms (5)

BCMA-TGFβ CAR-T cells (0.50 x 10^6 cells/kg)

EXPERIMENTAL

BCMA-TGFβ CAR-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of four dose levels of BCMA-TGFβ CAR-T cells based on the dose escalation design.

Biological: BCMA-TGFβ CAR-T cells (0.50 x 10^6 cells/kg)

BCMA-TGFβ CAR-T cells (0.75 x10^6 cells/kg)

EXPERIMENTAL

BCMA-TGFβ CAR-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of four dose levels of BCMA-TGFβ CAR-T cells based on the dose escalation design.

Biological: BCMA-TGFβ CAR-T cells (0.75 x10^6 cells/kg)

BCMA-TGFβ CAR-T cells (1 x 10^6 cells/kg)

EXPERIMENTAL

BCMA-TGFβ CAR-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of four dose levels of BCMA-TGFβ CAR-T cells based on the dose escalation design.

Biological: BCMA-TGFβ CAR-T cells (1 x 10^6 cells/kg)

BCMA-TGFβ CAR-T cells (2.5 x 10^6 cells/kg)

EXPERIMENTAL

BCMA-TGFβ CAR-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of four dose levels of BCMA-TGFβ CAR-T cells based on the dose escalation design.

Biological: BCMA-TGFβ CAR-T cells (2.5 x 10^6 cells/kg)

BCMA-TGFβ CAR-T cells (Maximum tolerated dose)

EXPERIMENTAL

After the maximal tolerated dose (MTD) is determined, an additional dose-expansion cohort of up to 9 patients (3 BCMA-naïve and 6 BCMA exposed) may be enrolled at that dose.

Biological: BCMA-TGFβ CAR-T cells (0.50 x 10^6 cells/kg); Biological: BCMA-TGFβ CAR-T cells (0.75 x10^6 cells/kg); Biological: BCMA-TGFβ CAR-T cells (1 x 10^6 cells/kg); Biological: BCMA-TGFβ CAR-T cells (2.5 x 10^6 cells/kg); Biological: Maximum tolerated dose

Interventions

BCMA-TGFβ CAR-T cells (0.50 x 10^6 cells/kg) BIOLOGICAL

This is dose level 0 (de-escalation).

BCMA-TGFβ CAR-T cells (0.50 x 10^6 cells/kg); BCMA-TGFβ CAR-T cells (Maximum tolerated dose)

BCMA-TGFβ CAR-T cells (0.75 x10^6 cells/kg) BIOLOGICAL

This is dose level 1, the starting dose.

BCMA-TGFβ CAR-T cells (0.75 x10^6 cells/kg); BCMA-TGFβ CAR-T cells (Maximum tolerated dose)

BCMA-TGFβ CAR-T cells (1 x 10^6 cells/kg) BIOLOGICAL

This is dose level 2.

BCMA-TGFβ CAR-T cells (1 x 10^6 cells/kg); BCMA-TGFβ CAR-T cells (Maximum tolerated dose)

BCMA-TGFβ CAR-T cells (2.5 x 10^6 cells/kg) BIOLOGICAL

This is dose level 3.

BCMA-TGFβ CAR-T cells (2.5 x 10^6 cells/kg); BCMA-TGFβ CAR-T cells (Maximum tolerated dose)

Maximum tolerated dose BIOLOGICAL

The maximum tolerated dose is yet to be determined.

BCMA-TGFβ CAR-T cells (Maximum tolerated dose)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be aged ≥18 years to 80 years old.
• Patients must have received three prior lines of therapies, including proteasome inhibitor, immunomodulator and a cluster of differentiation (CD) 38 monoclonal antibody:
• International Myeloma Working Group (IMWG) criteria defines refractory disease as disease progression on or within 60 days of receiving therapy.
• Patients must have measurable disease, including at least one or more of the following criteria:
• Serum M-protein ≥0.5 g/dl;
• Urine M-protein ≥200 mg/24 hrs;
• Involved serum light chain ≥100 mg/L with abnormal light chain ratio;
• Absolute CD 3 count ≥50 mm\^3.
• Karnofsky performance score ≥70.
• Adequate hepatic function, defined as:
• aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase \<3x upper limit of normal (ULN);
• Serum bilirubin \<2.0 mg/dL except for patients with Gilbert's syndrome, who must have serum bilirubin of \<3 mg/dL.
• Absolute neutrophil count (ANC) ≥1,000 with no Granulocyte colony-stimulating factor (G-CSF) within 72 hours or pegylated G-CSF within 10 days.
• Platelets ≥50,000/µL with no transfusion within 72 hours of eligibility testing.
• Adequate renal function, defined as creatinine clearance ≥50 mL/min calculated using the Cockroft-Gault formula.

You may not qualify if:

• Positive beta- Human chorionic gonadotropin (HCG) in female of child-bearing potential defined as per the Schedule of Events table.
• Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
• History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily.
• Presence of ≥ Grade 3 non-hematologic toxicities as per CTCAE version 5.0 from any previous treatment unless it is felt to be due to underlying disease.
• Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution. Minimum of 14 days or 5 half-lives of the drug (whichever is shorter) washout prior to apheresis.
• Refusal to participate in the long-term follow-up protocol.
• Patients with active central nervous system (CNS) involvement by malignancy on MRI or by lumbar puncture.
• a. Patients with prior CNS disease that has been effectively treated will be eligible providing last treatment was ≥2 weeks before apheresis and a remission documented within 4 weeks of planned CAR T-cell infusion by MRI brain and CSF analysis.
• Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are excluded if they are \<6 months post-transplant, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
• Plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, and AL amyloidosis.
• Prior treatment with gene therapy or any gene modified cellular therapy (only permitted in cohort B for the dose expansion phase).
• Prior BCMA-directed therapy (only permitted in cohort B for the dose expansion phase).
• Cytotoxic chemotherapy, oral chemotherapeutic agents, or antibody-directed treatment within 14 days of apheresis or after apheresis.
• Corticosteroids are allowable up until 7 days prior to apheresis and after apheresis for disease control up until the day prior to cell infusion (Day -1).
• Radiation is allowed to a single symptomatic site.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Related Publications (1)

• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.

  PMID: 30592986 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Maximum Tolerated Dose

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)

Toxicity Tests; Investigative Techniques; Toxicological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Officials

• Binod Dhakal, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 28, 2023
• First Posted: August 4, 2023
• Study Start: March 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share