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Recurrent Plasma Cell MyelomaPhase 1NCT03338972

Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma

A Phase 1 study testing Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143, Cyclophosphamide and Fludarabine in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
29 Nov 2017to 22 Mar 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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
  • Male and female patients of reproductive potential must be willing to use an effect contraceptive method before, during, and for at least 4 months after the CAR T cell infusion

Who cannot join

  • 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
Show all 28Show fewer
  • 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
  • Experimental agents within 4 weeks of leukapheresis unless progression is documented on therapy and at least 3 half-lives have elapsed prior to leukapheresis
  • Absolute neutrophil count (ANC) < 1000/mm^3, or per PI discretion if cytopenia thought to be related to underlying myeloma.
  • Hemoglobin (Hgb) < 8 mg/dl, or per PI discretion if cytopenia thought to be related to underlying myeloma.
  • Platelet count < 50,000/mm^3, or per PI discretion if cytopenia thought to be related to underlying myeloma.
  • Active autoimmune disease requiring immunosuppressive therapy
  • Major organ dysfunction defined as:
  • Creatinine clearance < 20 ml/min
  • Significant hepatic dysfunction (serum glutamic-oxaloacetic transaminase [SGOT] > 5 x upper limit of normal; bilirubin > 3.0 mg/dL)
  • Forced expiratory volume in 1 second (FEV1) of < 50% predicted or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% (patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing)
  • Anticipated survival of < 3 months
  • Contraindication to cyclophosphamide or fludarabine chemotherapy
  • Patients with known AL subtype amyloidosis
  • Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the PI; or unwillingness or inability to follow the procedures required in the protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety of adoptive therapy with ex vivo expanded autologous CD8+ plus CD4+ T cells transduced to express a human B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) for patients with relapsed or treatment refractory multiple myeloma.

SECONDARY OBJECTIVES:

  1. To determine the duration of in vivo persistence and the phenotype of long lived CAR-T cells.

II. To determine the degree to which adoptively transferred T cells traffic to multiple myeloma (MM) cells in the bone marrow (BM) and function in vivo.

III. To estimate the antitumor activity of adoptively transferred BCMA-specific CAR-expressing T lymphocytes (BCMA CAR-T cells).

OUTLINE: This is a dose-escalation study of BCMA-specific CAR-expressing T lymphocytes.

Patients undergo leukapheresis to obtain their immune cells, from which CAR-T cells are produced. A few weeks later, patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning 36-96 hours after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes intravenously (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).

After completion of study treatment, patients are followed up at 60, 90, 120, 180, and 365 days and then annually up to 15 years.

Being tested
Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143, Cyclophosphamide, Fludarabine, Leukapheresis
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143Biological

    Also called Autologous Anti-BCMA-CAR CD4+/CD8+ Cells, Autologous Anti-BCMA-CAR-expressing CD8+ and CD4+ T-lymphocytes, BCMA CAR-CD4+/CD8+ T-cells, BCMA-specific CAR-expressing CD4+/CD8+ T-lymphocytes

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

Study groups in NCT03338972
Study groupRoleWhat they receive
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 1ExperimentalPatients 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)
Receives: Biological: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 2ExperimentalPatients 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)
Receives: Biological: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 3ExperimentalPatients 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)
Receives: Biological: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis
Treatment (chemotherapy, BCMA CAR-T cells) at dose level 4ExperimentalPatients 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)
Receives: Biological: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days after CAR T cell infusion

  2. 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.

    Measured: Up to 28 days after CAR T-cell infusion

Secondary outcomes (5)

  1. Duration of Persistence of Adoptively Transferred BCMA CAR-T Cells

    Persistence of CART cells is tested by qPCR in PBMC.

    Measured: Assessed from Baseline up to a maximum of 537 days

  2. Number of Participants With Detectable BCMA CART Cell Migration to Primary Disease Site (Bone Marrow) at Day 28

    Measured: Baseline up to Day 28

  3. Objective Response Rate (ORR)

    Number of patients with a best response of either complete response, stringent complete response, very good partial response or partial response, assessed using modified International Myeloma Working group response criteria.

    Measured: Baseline up to 3 months after CART infusion

  4. Progression-free Survival (PFS)

    Outcome is reported as the count of participants who were alive at the 1 year post treatment mark and did not experience disease progression by the 1 year post treatment mark.

    Measured: Assessed up to 1 year after CART infusion

  5. Overall Survival (OS)

    Outcome is reported as a count of participants who were alive at the 1 year post-infusion timepoint.

    Measured: Assessed up to 1 year after CART infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2017
  2. Study start29 Nov 2017
  3. Primary completion3 May 2021
  4. Study completion22 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03338972
Sponsor's protocol ID
9762
Other IDs
NCI-2017-01932, 9762, RG9217023, P01CA018029
Status last verified
Aug 2023
First submitted
7 Nov 2017
Last updated
8 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40198877

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143, Cyclophosphamide and Fludarabine in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicities (DLT) Rate (time frame: Up to 28 days after CAR T cell infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03338972, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2023.

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