Adoptive Transfer of MUC1 Activated T Cells for the Treatment of MUC1 Positive Recurrent or Refractory Multiple Myeloma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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.
  • - 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.
  • - Expected survival unless investigational therapy is effective is 3-5 months.
  • - 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 specimens and bone marrow biopsy tissue 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.

Exclusion Criteria:

  • - 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.
  • - 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 Details

Trial ID:

This trial id was obtained from, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Mayo Clinic
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Leif Bergsagel
Principal Investigator Affiliation Mayo Clinic Hospital in Arizona
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma
Additional Details


  • I. To determine the toxicity of in-house, manufactured MUC1-activated T cells in patients with relapsed/refractory MUC1-expressing multiple myeloma.
  • I. 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.
  • V. Assess efficacy of a single dose of MUC1-activated T cells.
  • I. 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.
  • V. 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.

Arms & Interventions


Experimental: Treatment (cyclophosphamide, MUC1-activated T-cells)

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.


Biological: - Autologous MUC1-activated T-cells

Given IV

Drug: - Cyclophosphamide

Given IV

Contact a Trial Team

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Mayo Clinic Hospital in Arizona, Phoenix, Arizona




Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054

Site Contact

Clinical Trial Referral Office