Overview

Genetically Engineered Cells (MUC1-Activated T-Cells) for the Treatment of MUC1 Positive Recurrent or Refractory Multiple Myeloma

Status:
Not yet recruiting
Trial end date:
2025-04-01
Target enrollment:
0
Participant gender:
All
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. 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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Mayo Clinic
Collaborator:
National Cancer Institute (NCI)
Treatments:
Cyclophosphamide
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.