Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma
A Phase I Study of Adoptive Immunotherapy for Advanced B-Cell Maturation Antigen (BCMA)+ Multiple Myeloma With Autologous CD4+ and CD8+ T Cells Engineered to Express a BCMA-Specific Chimeric Antigen Receptor
4 other identifiers
interventional
28
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of BCMA CAR-T cells in treating patients with BCMA positive multiple myeloma that has come back or does not respond to treatment. T cells are a type of white blood cell and a major component of the immune system. T-cells that have been genetically modified in the laboratory express BCMA and may kill cancer cells with the protein BCMA on their surface. Giving chemotherapy before BCMA CAR-T cells may reduce the amount of disease and to cause a low lymphocyte (white blood cell) count in the blood, which may help the infused BCMA CAR-T cells survive and expand.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Nov 2017
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 7, 2017
CompletedFirst Posted
Study publicly available on registry
November 9, 2017
CompletedStudy Start
First participant enrolled
November 29, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 3, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 22, 2022
CompletedResults Posted
Study results publicly available
August 5, 2022
CompletedSeptember 8, 2023
August 1, 2023
3.4 years
November 7, 2017
April 26, 2022
August 15, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
Dose-limiting Toxicities (DLT) Rate
Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Outcome will be reported as count of participants in each arm who experienced a DLT. No patients received more than one CAR T cell infusion, so DLT assessment period was only 28 days after first and only CAR T infusion for all patients.
Up to 28 days after CAR T cell infusion
Count of Patients That Experienced Adverse Events
Toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 No patients received more than one CAR T cell infusion, so AE assessment period was only 28 days after first and only CAR T infusion for all patients.
Up to 28 days after CAR T-cell infusion
Secondary Outcomes (5)
Duration of Persistence of Adoptively Transferred BCMA CAR-T Cells
Assessed from Baseline up to a maximum of 537 days
Number of Participants With Detectable BCMA CART Cell Migration to Primary Disease Site (Bone Marrow) at Day 28
Baseline up to Day 28
Objective Response Rate (ORR)
Baseline up to 3 months after CART infusion
Progression-free Survival (PFS)
Assessed up to 1 year after CART infusion
Overall Survival (OS)
Assessed up to 1 year after CART infusion
Study Arms (4)
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 1
EXPERIMENTALPatients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator). Arm 1 contains patients treated as dose level 1 (50 x 10\^6 EGFRt cells)
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 2
EXPERIMENTALPatients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator). Arm 2 contains patients treated as dose level 2 (150 x 10\^6 EGFRt cells)
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 3
EXPERIMENTALPatients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator). Arm 3 contains patients treated as dose level 3 (300 x 10\^6 EGFRt cells)
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 4
EXPERIMENTALPatients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator). Arm 4 contains patients treated as dose level 4 (450 x 10\^6 EGFRt cells)
Interventions
Given IV
Given IV
Given IV
Undergo leukapheresis
Eligibility Criteria
You may qualify if:
- Have the capacity to give informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status score =\< 2.
- Have measurable disease by International Myeloma Working Group (IMWG) criteria based on one or more of the following findings:
- Serum M-protein \>= 1 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%
- Have a diagnosis of BCMA+ MM (\>= 5% BCMA+ by flow cytometry on CD138 co-expressing plasma cells obtained within 45 days of study enrollment); the MM diagnosis must be confirmed by internal pathology review of a fresh biopsy specimen at the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)
- Have relapsed or treatment refractory disease with \>= 10% CD138+ malignant plasma cells (IHC) on BM core biopsy, either:
- Following autologous stem cell transplant (ASCT)
- Or, if a patient has not yet undergone ASCT, the individual must:
- Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician and principal investigator and,
- Demonstrate disease that persists after \> 4 cycles of induction therapy and that is double refractory (persistence/progression) after therapy with both a proteasome inhibitor and immunomodulatory drug (IMiD) administered either in tandem, or in sequence; \> 4 cycles of therapy are not required for patients with a diagnosis of plasma cell leukemia
- Patients receiving retreatment do not need to meet the \> 10% CD138+ malignant plasma cells (immunohistochemistry staining method \[IHC\]) on BM core biopsy
- +1 more criteria
You may not qualify if:
- History of another primary malignancy that requires intervention beyond surveillance or that has not been in remission for at least 1 year (the following are exempt from the 1 year limit: non-melanoma skin cancer, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on papanicolaou \[PAP\] smear)
- Active hepatitis B, hepatitis C at the time of screening
- Patients who are (human immunodeficiency virus \[HIV\]) seropositive
- Subjects with uncontrolled active infection
- \> 1 hospital admission (lasting 5 days or more) for documented infection in prior 6 months
- Presence of acute or chronic graft-versus-host disease (GVHD) requiring active treatment unless limited to skin involvement and managed with topical steroid therapy alone
- History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease as determined by the principal investigator (PI) or designee
- History of clinically relevant or active central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis, active central nervous system MM involvement and/or carcinomatous meningitis; subjects with previously treated central nervous systems involvement may participate, provided they are free of disease in the CNS (documented by flow cytometry performed on the cerebrospinal fluid \[CSF\] within 14 days of enrollment) and have no evidence of new sites of CNS activity
- Pregnant or breastfeeding females
- Allogeneic HSCT or donor lymphocyte infusion within 90 days of leukapheresis.
- Use of any of the following:
- Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis; physiologic replacement, topical, and inhaled steroids are permitted
- Cytotoxic chemotherapeutic agents within 1 week of leukapheresis; oral chemotherapeutic agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis
- Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis
- Daratumumab (or other anti-CD38 therapy) within 30 days of leukapheresis
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (1)
Tuazon SA, Portuguese AJ, Pont MJ, Cowan AJ, Cole GO, Sather BD, Song X, Thomas S, Wood BL, Blake M, Works MG, Shadman M, Liang EC, Wu QV, Voutsinas JM, Gooley TA, Turtle CJ, Till BG, Coffey DG, Maloney DG, Riddell SR, Green DJ. A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up. Blood. 2025 Jul 31;146(5):535-545. doi: 10.1182/blood.2024027681.
PMID: 40198877DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Damian Green
- Organization
- Fred Hutchinson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Damian J. Green
Fred Hutch/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
November 7, 2017
First Posted
November 9, 2017
Study Start
November 29, 2017
Primary Completion
May 3, 2021
Study Completion
March 22, 2022
Last Updated
September 8, 2023
Results First Posted
August 5, 2022
Record last verified: 2023-08