Recurrent Plasma Cell MyelomaPhase 1NCT05411497
Genetically Engineered Cells (MUC1-Activated T-Cells) for the Treatment of MUC1 Positive Recurrent or Refractory Multiple Myeloma
A Phase 1 study testing Autologous MUC1-activated T-cells and Cyclophosphamide in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.
Trial summary
This phase I trial tests the safety, side effects and best dose of MUC1-activated T cells in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory) and is positive for expression of the MUC1 protein. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
- What is being tested?
- Autologous MUC1-activated T-cells and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Jun 2022to 18 Aug 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- MUC1 expression in multiple myeloma tumor cells verified by immunohistochemistry (IHC) or flow cytometry (FCM). Heterogeneous tumor expression of MUC1 is acceptable
- Relapsed or refractory multiple myeloma previously treated with or intolerant to at least three prior lines of therapy and be relapsed or intolerant to a proteasome inhibitor, an immune modulatory drug (IMiD), and a CD38 antibody. Patients must be at least 90 days since an autologous stem cell transplant, if performed
- Patients must have measurable disease per IMWG criteria on study entry, which must include at least one of the following:
- Serum M-spike >= 0.5 g/dL Patients with IgA, IgM or IgD myeloma in whom serum protein electrophoresis is deemed unreliable for routine M-protein quantitation may be considered eligible if total serum IgA, IgM or IgD level is elevated above normal range and parallels disease course
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- 24-hour urine M-spike >= 200 mg
- Involved serum free light chain (FLC) >= 10 mg/L with an abnormal free light chain ratio
- Bone marrow plasma cells > 30%
- Patients with extramedullary disease:
- 1 lesion that has a single diameter of >= 2 cm measured by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT
- Skin lesions can be used if the area is >= 2cm in at least one diameter and measured with a ruler
- Willingness and ability to provide written informed consent
- Willing to return to Mayo Clinic Hospital in Arizona (MCA) for follow-up during the active monitoring phase of the study
- Willingness to provide mandatory blood, bone marrow biopsy, and aspirate specimens for correlative research
- Willing to undergo leukapheresis for blood component collection
- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of study registration)
- Lymphocyte count >= 500/mm^3 (within 14 days of study registration)
- Hemoglobin >= 8.0 g/dL (within 14 days of study registration)
- Platelet count >= 30,000/mm^3 (within 14 days of study registration)
- Total bilirubin =< 2.0 mg/dL unless patient has documented Gilbert's syndrome (Subjects with Gilbert's Syndrome may be included if their total Bilirubin is =< 3.0 x upper limit of normal (ULN) and direct bilirubin =< 1.5 x ULN) (within 14 days of study registration)
- Alanine aminotransferase (ALT) and aspartate amino transferase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement of their cancer) (within 14 days of study registration)
- Prothrombin time, international normalized ratio (PT, INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulation therapy and INR or aPTT is within target range of therapy (for patients receiving anticoagulation, there should be no prior history of bleeding and no recent deep vein thrombosis [DVT]/pulmonary embolism [PE] within the last 6 months of enrollment)
- Calculated creatinine clearance >= 30 ml/min using the Cockcroft-Gault formula (within 14 days of study registration)
- Baseline oxygen saturation >= 90% on room air
Who cannot join
- Clinically unresolved central nervous system (CNS) metastases
- Prior treatment targeting MUC1
- Subjects with known plasma cell leukemia (PCL)
- Any of the following are excluded because this study involves an agent (CTX) that has known genotoxic, mutagenic and/or teratogenic effects:
- Pregnant persons
- Nursing persons
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- Persons of childbearing potential who are unwilling to employ adequate birth control measures
- History of myocardial infarction >= 6 months prior to registration, and/or congestive heart failure requiring ongoing treatment such as medications and/or an implanted defibrillator to control life-threatening arrhythmias.
- Failure to recover to grade 1 or baseline from acute, reversible effects of prior therapy regardless of interval since last treatment.
- EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment.
- Uncontrolled concurrent illness including, but not limited to:
- Inability to clear an ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled psychiatric problems and/or difficult social situation
- Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- Any other conditions that the protocol investigators deem could potentially limit compliance with study requirements
- Evidence of clinical immunocompromise and/or human immunodeficiency virus (HIV) positivity and currently receiving antiretroviral therapy
- Patients requiring chronic supraphysiologic daily doses of steroids (>10 mg prednisone or prednisolone, >= 4 mg Decadron or >= 50 mg hydrocortisol daily)
- Patients receiving any other investigational agent which could be considered a treatment for the neoplasm
- Other active malignancy first documented =< 4 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of other malignancy, the patient must not be receiving other treatment aimed at suppressing its recurrence.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: Use of Natural Signals and Ambient Dendritic Cells to Culture-Expand Cancer Targeting T-Cells Directly From Unfractionated Peripheral Blood: A Phase 1 T-Cell Dose Escalation Trial Targeting Relapsed and Refractory MUC1-Expressing Multiple Myeloma
This phase I trial tests the safety, side effects and best dose of MUC1-activated T cells in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory) and is positive for expression of the MUC1 protein. T-cells are infection fighting blood cells that can kill cancer cells. MUC1-activated T-cells are made from the body's own T cells. The manufactured T-cells are made to target the MUC1 genetic marker and may help the body's immune system identify and kill cancer cells.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the toxicity of in-house, manufactured MUC1-activated T cells in patients with relapsed/refractory MUC1-expressing multiple myeloma.
SECONDARY OBJECTIVES:
- Obtain preliminary efficacy associated with MUC1-targeting peripheral blood mononuclear cells (PBMC) derived T cells in conjunction with cyclophosphamide (CTX) in MUC1-expressing multiple myeloma patients.
Ia. Assess best objective response observed based on International Myeloma Working Group (IMWG) criteria and duration of any partial or complete responses (partial response [PR] or complete response [CR]).
Ib. Assess progression-free (PFS) and overall (OS) survival. II. Determine feasibility of production and administration of MUC1-targeting PBMC-derived T cells and ability to proceed with T cell dose escalation.
IIa. Assess the feasibility of in-house preparation of in vitro-sensitized T cells.
III. Evaluate the safety, including all grades of neurotoxicity immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) as determined by American Society of Transplantation and Cell Therapy (ASTCT) criteria, by monitoring adverse events, laboratory abnormalities, vital signs, and other safety parameters.
IV. Estimate the incidence of Grade 3 or higher of neurotoxicity and cytokine release syndrome by Grade 3 or higher neurotoxicity (ICANS) or CRS per the ASTCT criteria.
- Assess efficacy of a single dose of MUC1-activated T cells.
CORRELATIVE RESEARCH OBJECTIVES:
- Perform analyses of Vbeta usage by T cell receptors (TCR) to see whether culture expansion generated TCR oligoclonality; whether such T cells persist in the circulation following adoptive transfer; and whether such persistence significantly correlates to objective responses.
Ia. Levels of Vbeta alleles on CD3+ T cells in blood by antibody staining or deoxyribonucleic acid (DNA) sequencing (Adaptive Biotechnologies).
II. Characterize the changes in cytokine levels over time. III. Determine whether T cells recognizing MUC1 in an major histocompatibility complex (MHC)-restricted manner in culture (intracellular IFN-gamma assays) correspond to therapeutic efficacy upon subsequent adoptive transfer.
IV. Determine the immune phenotype of the immune cells, the inhibitory profile, and transcription factors using multi-color flow cytometry.
- Assess hospital resource utilization and health economics.
OUTLINE: This is a dose-escalation study of MUC1-activated T-cells.
LYMPHODEPLETION (LD) CHEMOTHERAPY : Patients receive cyclophosphamide intravenously (IV) over 60 minutes on days -5, -4, -3.
AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT): Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0.
After completion of study treatment, patients are followed up on days 1, 2, 3, 7, 28 and every 90 days for up to 2 years.
- Being tested
- Autologous MUC1-activated T-cells, Cyclophosphamide
- 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 MUC1-activated T-cellsBiological
Also called Autologous MUC1-activated 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
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cyclophosphamide, MUC1-activated T-cells) | Experimental | LD CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes on days -5, -4, -3.
ASCT: Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0. Receives: Biological: Autologous MUC1-activated T-cells; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: Up to 4 years
Secondary outcomes (3)
Clinical response
The number of responses (complete response [CR], very good partial response [VGPR], partial response [PR], or minimal response [MR]) will be summarized by simple descriptive summary statistics. Assuming that the number of responses is binomially distributed, we will estimate the proportion of patients who achieve an overall as well as specific type of response along with corresponding 95% exact binomial confidence intervals.
Measured: Up to 4 years
Progression-free survival
The distribution of survival time will be estimated using the method of Kaplan-Meier (overall and by dose level). Given the nature of phase I trials and the limited numbers, this endpoint will be primarily descriptive and to characterize the patients enrolled.
Measured: From registration to disease progression or death due to any cause, assessed up to 4 years
Overall survival
The distribution of survival time will be estimated using the method of Kaplan-Meier (overall and by dose level).
Measured: From registration to death due to any cause, assessed up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2022
- Study start20 Jun 2022
- Primary completion18 Aug 2027 (estimated)
- Study completion18 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leif Bergsagel, M.D., Principal investigator, Mayo Clinic Hospital in Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05411497
- Sponsor's protocol ID
- MC200806
- Other IDs
- 21-001202
- Status last verified
- Apr 2026
- First submitted
- 19 May 2022
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Natural Signals and Ambient Dendritic Cells to Culture-Expand Cancer Targeting T-Cells Directly From Unfractionated Peripheral Blood: A Phase 1 T-Cell Dose Escalation Trial Targeting Relapsed and Refractory MUC1-Expressing Multiple Myeloma
- ClinicalTrials.gov ID
- NCT05411497
- Acronym / sponsor ID
- MC200806
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 20 Jun 2022 (actual)
- Primary completion
- 18 Aug 2027 (estimated)
- Study completion
- 18 Aug 2027 (estimated)
- First posted
- 9 Jun 2022 (actual)
- 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.
This phase I trial tests the safety, side effects and best dose of MUC1-activated T cells in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory) and is positive for expression of the MUC1 protein. T-cells are infection fighting blood cells that can kill cancer cells. MUC1-activated T-cells are made from the body's own T cells. The manufactured T-cells are made to target the MUC1 genetic marker and may help the body's immune system identify and kill cancer cells.
Detailed description
PRIMARY OBJECTIVE:
- To determine the toxicity of in-house, manufactured MUC1-activated T cells in patients with relapsed/refractory MUC1-expressing multiple myeloma.
SECONDARY OBJECTIVES:
- Obtain preliminary efficacy associated with MUC1-targeting peripheral blood mononuclear cells (PBMC) derived T cells in conjunction with cyclophosphamide (CTX) in MUC1-expressing multiple myeloma patients.
Ia. Assess best objective response observed based on International Myeloma Working Group (IMWG) criteria and duration of any partial or complete responses (partial response [PR] or complete response [CR]).
Ib. Assess progression-free (PFS) and overall (OS) survival. II. Determine feasibility of production and administration of MUC1-targeting PBMC-derived T cells and ability to proceed with T cell dose escalation.
IIa. Assess the feasibility of in-house preparation of in vitro-sensitized T cells.
III. Evaluate the safety, including all grades of neurotoxicity immune effector cell associated neurotoxicity (ICANS) and cytokine release syndrome (CRS) as determined by American Society of Transplantation and Cell Therapy (ASTCT) criteria, by monitoring adverse events, laboratory abnormalities, vital signs, and other safety parameters.
IV. Estimate the incidence of Grade 3 or higher of neurotoxicity and cytokine release syndrome by Grade 3 or higher neurotoxicity (ICANS) or CRS per the ASTCT criteria.
- Assess efficacy of a single dose of MUC1-activated T cells.
CORRELATIVE RESEARCH OBJECTIVES:
- Perform analyses of Vbeta usage by T cell receptors (TCR) to see whether culture expansion generated TCR oligoclonality; whether such T cells persist in the circulation following adoptive transfer; and whether such persistence significantly correlates to objective responses.
Ia. Levels of Vbeta alleles on CD3+ T cells in blood by antibody staining or deoxyribonucleic acid (DNA) sequencing (Adaptive Biotechnologies).
II. Characterize the changes in cytokine levels over time. III. Determine whether T cells recognizing MUC1 in an major histocompatibility complex (MHC)-restricted manner in culture (intracellular IFN-gamma assays) correspond to therapeutic efficacy upon subsequent adoptive transfer.
IV. Determine the immune phenotype of the immune cells, the inhibitory profile, and transcription factors using multi-color flow cytometry.
- Assess hospital resource utilization and health economics.
OUTLINE: This is a dose-escalation study of MUC1-activated T-cells.
LYMPHODEPLETION (LD) CHEMOTHERAPY : Patients receive cyclophosphamide intravenously (IV) over 60 minutes on days -5, -4, -3.
AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT): Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0.
After completion of study treatment, patients are followed up on days 1, 2, 3, 7, 28 and every 90 days for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cyclophosphamide, MUC1-activated T-cells) | Experimental | Biological: Autologous MUC1-activated T-cells, Drug: CyclophosphamideLD CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes on days -5, -4, -3. ASCT: Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- MUC1 expression in multiple myeloma tumor cells verified by immunohistochemistry (IHC) or flow cytometry (FCM). Heterogeneous tumor expression of MUC1 is acceptable
- Relapsed or refractory multiple myeloma previously treated with or intolerant to at least three prior lines of therapy and be relapsed or intolerant to a proteasome inhibitor, an immune modulatory drug (IMiD), and a CD38 antibody. Patients must be at least 90 days since an autologous stem cell transplant, if performed
- Patients must have measurable disease per IMWG criteria on study entry, which must include at least one of the following:
Key exclusion criteria (21 listed)
- Clinically unresolved central nervous system (CNS) metastases
- Prior treatment targeting MUC1
- Subjects with known plasma cell leukemia (PCL)
- Any of the following are excluded because this study involves an agent (CTX) that has known genotoxic, mutagenic and/or teratogenic effects:
- History of myocardial infarction >= 6 months prior to registration, and/or congestive heart failure requiring ongoing treatment such as medications and/or an implanted defibrillator to control life-threatening arrhythmias.
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 |
|---|---|---|
| Autologous MUC1-activated T-cellsAlso: Autologous MUC1-activated T-lymphocytesGiven IV | Biological | Treatment (cyclophosphamide, MUC1-activated T-cells) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Treatment (cyclophosphamide, MUC1-activated T-cells) |
Primary outcome
Incidence of adverse events
Time frame: Up to 4 years
3 secondary outcomes
Clinical response
Time frame: Up to 4 years
Progression-free survival
Time frame: From registration to disease progression or death due to any cause, assessed up to 4 years
Overall survival
Time frame: From registration to death due to any cause, assessed up to 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Leif Bergsagel, M.D. principal investigator
Mayo Clinic Hospital in Arizona
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous MUC1-activated T-cells and Cyclophosphamide in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by Mayo Clinic at 2 sites 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 25 inclusion and 21 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: under way, not looking for participants, as of the sponsor's last update on 3 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of adverse events (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Apr 2026.