Los requisitos de elegibilidad de los participantes incluyen la edad, el sexo, el tipo y el estadio de la enfermedad, y los problemas de salud o tratamientos previos. Las pautas difieren de un estudio a otro e identifican quiénes pueden o no pueden participar. No hay garantía de que cada persona elegible que desee participar en un ensayo se inscribirá. Comunícate con el equipo del estudio para analizar la elegibilidad del estudio y la posible participación.
3.1 Pre-registration – Inclusion Criteria
3.1.1 Age ≥18 years
3.1.2 ECOG Performance Status (PS) 0-1 (Appendix I).
3.1.3 Patients must have biopsy-proven MUC1+ relapsed or refractory multiple myeloma.
3.1. 4 The patient must have 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.
3.1.5 Patients must have measurable disease per IMWG criteria on study entry, which must include at least one of the following:
a. Serum M-spike ≥ 0.5 g/dL
b. 24-hour urine M-spike ≥ 200 mg
c. Involved serum free light chain (FLC) ≥ 50 mg/L
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 if total serum IgA level is elevated above normal range and parallels disease course.
3.1.6 The patient should not have received prior treatment attempting to target MUC1.
3.1.7 Expected survival unless investigational therapy is effective is 3-5 months
3.1.8 Willingness and ability to provide written informed consent.
3.1.9 Willing to return to MCA for follow-up during the Active Monitoring Phase of the study.
3.1.10 Willingness to provide mandatory blood specimens or tissue for correlative research (see Section 14.0).
3.1.11 Willing to undergo leukapheresis for blood component collection.
3.1.12 The following laboratory parameters (paid by patient insurance) must be performed ≤14 days prior to registration:
- Absolute neutrophil count (ANC) ≥1500/mm3
- Lymphocyte count ≥ 500/mm3
- Hemoglobin ≥ 8.0 g/dL
- Platelet count ³30,000/mm3
- 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 ULN and direct bilirubin ≤1.5 x ULN)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) £3 x ULN (≤5 x ULN for patients with liver involvement of their cancer)
- PT/INR/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 DVT/PE within the last 6 months of enrollment)
- Calculated creatinine clearance ≥30 ml/min using the Cockcroft-Gault formula below:
Cockcroft-Gault Equation:
Creatinine clearance for males = (140 - age)(weight in kg)
(72)(serum creatinine in mg/dL)
Creatinine clearance for females = (140 - age)(weight in kg)(0.85)
(72)(serum creatinine in mg/dL)
3.1.13 Patients must cooperate in obtaining immunohistochemical (IHC) evidence that their own cancer expresses MUC1. This requirement can be met in several different ways:
- Bone marrow biopsy that will be sent to NeoGenomics (Aliso Viejo, CA) for overnight immunohistochemical (IHC) confirmation that the tumor actively expresses MUC1.
- Plasma cells in the blood or bone marrow expressing MUC1 by flow cytometry.
3.1.15 Baseline oxygen saturation ≥90% on room air
3.2 Pre-registration - Exclusion criteria
3.2.1 Clinically unresolved CNS metastases
3.2.2 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
3.2.2 History of myocardial infarction ≤6 months prior to pre-registration, and/or congestive heart failure requiring ongoing treatment such as medications and/or an implanted defibrillator to control life-threatening arrhythmias.
3.2.3 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.
3.2.4 Uncontrolled concurrent illness including, but not limited to:
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- 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
3.2.5 Evidence of clinical immunocompromise and/or HIV positivity and currently receiving antiretroviral therapy
3.2.6 Patients requiring chronic supraphysiologic daily doses of steroids (>10 mg prednisone or prednisolone, ≥ 4 mg Decadron or ≥ 50 mg hydrocortisol daily).
3.2.7 Patients receiving any other investigational agent which could be considered a treatment for the neoplasm.
3.2.8 Other active malignancy first documented ≤ 4 years prior to pre-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.
3.3 Registration - Inclusion Criteria
3.3.1 Patient continues to meet pre-registration inclusion criteria.
3.3.2 IHC verification that patient’s cancer expressed MUC1. Heterogeneous tumor expression of MUC1 is acceptable, see section 17.0.
3.3.3 Because there will be a 3-4 week interval between leukapheresis and the harvest of cultured patient T-cells for autologous administration (i.e., adoptive transfer), bridging therapy can be performed so long as it is completed at least 2 weeks before infusion of the T-cells.
3.4 Registration - Exclusion Criteria
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- Patient continues to lack pre-registration exclusion criteria.
- Longer than 15 days between pre-registration and registration