Multiple MyelomaPhase 1NCT02546167
CART-BCMA Cells for Multiple Myeloma
A Phase 1 study testing CART-BCMA in people with Multiple Myeloma, run by University of Pennsylvania at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- CART-BCMA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Sep 2015to 27 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- OR
- 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".
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- 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.
- Subjects must have measurable disease on study entry, which must include at least 1 of the following:
- Serum M-spike ≥ 0.5 g/dL*
- 24 hr urine M-spike ≥ 200mg
- Involved serum FLC ≥ 50 mg/L with abnormal ratio
- Measurable plasmacytoma on exam or imaging
- Bone marrow plasma cells ≥ 20% (bone marrow biopsy only required at screening if no other measurable disease is present).
- Note: Patients with IgA myeloma in whom serum protein electrophoresis is deemed unreliable, due to co-migration of normal serum proteins with the paraprotein in the beta region, may be considered eligible as long as total serum IgA level is elevated above normal range.
- Subjects of reproductive potential must agree to use acceptable birth control methods.
- IMWG Criteria for Diagnosis of Multiple Myeloma Presence of an M-component in serum and/or urine plus clonal plasma cells in the bone marrow and/or a documented clonal plasmacytoma. In patients with no detectable M-component, an abnormal serum FLC ratio on the serum FLC assay can substitute and satisfy this criterion. For patients, with no serum or urine M-component and normal serum FLC ratio, the baseline bone marrow must have ≥10% clonal plasma cells; these patients are referred to as having 'non-secretory myeloma'. Patients with biopsy-proven amyloidosis and/or systemic light chain deposition disease (LCDD) should be classified as 'myeloma with documented amyloidosis' or 'myeloma with documented LCDD,' respectively if they have ≥30% plasma cells and/or myeloma-related bone disease.
- PLUS one or more of the following, which must be attributable to the underlying plasma cell disorder:
- Calcium elevation (>11.5 mg/dl)
- Renal insufficiency (creatinine >2 mg/dl)
- Anemia (hemoglobin <10 g/dl or at 2 g/dl below normal)
- Bone disease (lytic lesions or osteopenia) OR one of the following "myeloma-defining events"
- Bone marrow plasma cells ≥60% of cellularity
- Serum free kappa:lambda ratio ≥100:1 (or ≤1:100), with involved free light chain ≥100 mg/L
- More than 1 focal bone lesion on MRI
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pilot Study Of Redirected Autologous T Cells Engineered To Contain an Anti-BCMA scFv Coupled To TCRζ And 4-1BB Signaling Domains in Patients With Relapsed and/or Refractory Multiple Myeloma
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.
Read the detailed description
At entry subjects will undergo routine laboratory and imaging assessment of their multiple myeloma. Eligible subjects will undergo steady-state apheresis to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-BCMA manufacturing. Cryopreserved historical apheresis products collected from the patient prior to study entry are usable for CART-BCMA manufacturing if collected at an appropriately certified apheresis center and the product meets adequate mononuclear cell yields. If a historical apheresis product is not available, an apheresis procedure will be scheduled for cell procurement after study entry. The T cells will be purified from the PBMC, transduced with TCRζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration. The number of subjects who have inadequate T cell collections, expansion or manufacturing compared to the number of subjects who have CAR T cells successfully manufactured will be recorded; feasibility of product manufacturing is not expected to be problematic in this patient population.
- Conditions
- Multiple Myeloma
- Being tested
- CART-BCMA
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CART-BCMABiological
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | will receive 1-5x10^7 CART-BCMA cells given as a split dose infusion over 3 days. Receives: 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. Receives: 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. Receives: Biological: CART-BCMA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2015 (estimated)
- Study start3 Sep 2015
- Primary completion21 Aug 2019
- Study completion27 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adam Cohen, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02546167
- Sponsor's protocol ID
- UPCC 14415, 822756
- Status last verified
- Jun 2025
- First submitted
- 9 Sep 2015
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30896447Bu 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.
PubMed 29899820
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Of Redirected Autologous T Cells Engineered To Contain an Anti-BCMA scFv Coupled To TCRζ And 4-1BB Signaling Domains in Patients With Relapsed and/or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02546167
- Acronym / sponsor ID
- UPCC 14415, 822756
- Conditions
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 3 Sep 2015
- Primary completion
- 21 Aug 2019 (actual)
- Study completion
- 27 Jul 2020 (actual)
- First posted
- 10 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
At entry subjects will undergo routine laboratory and imaging assessment of their multiple myeloma. Eligible subjects will undergo steady-state apheresis to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-BCMA manufacturing. Cryopreserved historical apheresis products collected from the patient prior to study entry are usable for CART-BCMA manufacturing if collected at an appropriately certified apheresis center and the product meets adequate mononuclear cell yields. If a historical apheresis product is not available, an apheresis procedure will be scheduled for cell procurement after study entry. The T cells will be purified from the PBMC, transduced with TCRζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration. The number of subjects who have inadequate T cell collections, expansion or manufacturing compared to the number of subjects who have CAR T cells successfully manufactured will be recorded; feasibility of product manufacturing is not expected to be problematic in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: CART-BCMAwill receive 1-5x10^7 CART-BCMA cells given as a split dose infusion over 3 days. |
| Cohort 2 | Experimental | Biological: CART-BCMACyclophosphamide infusion prior to 1-5x10^7 CART BCMA cells given as a split dose infusion over 3 days. |
| Cohort 3 | Experimental | Biological: CART-BCMACyclophosphamide infusion prior to 1-5x10^8 CART BCMA cells given as a split dose infusion over 3 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- 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:
- OR
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CART-BCMA | Biological | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Number of Adverse Events
Time frame: 2 years
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Derived from this study: PubMed 30896447Cohen 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.
- Derived from this study: PubMed 29899820Bu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Cohen, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CART-BCMA in people with Multiple Myeloma, run by University of Pennsylvania 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 33 inclusion and 11 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 25 Jun 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of Adverse Events (time frame: 2 years). 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 NCT02546167, which also lists 2 linked publications.
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 25 Jun 2025; AzTrials last refreshed its copy on 3 Nov 2026.