Autologous CAR138 T-cells in Treating Patients with Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• PRIOR TO CELL PROCUREMENT: Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; subjects must sign a consent to undergo cell procurement
• PRIOR TO CELL PROCUREMENT: Age >= 18 years at the time of consent
• PRIOR TO CELL PROCUREMENT: Karnofsky score of >= 60%
• PRIOR TO CELL PROCUREMENT: Diagnosis of relapsed or refractory multiple myeloma (as defined by the Revised Uniform Response Criteria outlined by the IMWG (74)
• PRIOR TO CELL PROCUREMENT: Measurable disease as defined by one or more of the following within 60 days of cell procurement: 1) serum M-protein >= 1.0 g/dL (>= 0.5 g/dL for IgA myeloma); 2) urine M-protein >= 200 mg/24 hours; 3) involved serum free light chain level >= 10 mg/dL AND an abnormal serum free light chain ratio; subjects with non-secretory disease and a baseline marrow burden of myeloma of at least 30% will also be eligible to participate
• PRIOR TO CELL PROCUREMENT: Received at least 3 lines of prior chemotherapy; the prior regimens must have included an immunomodulatory agent (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) * Two lines of therapy will be allowed if the subjects has disease that is refractory to both an immunomodulatory agent (lenalidomide or pomalidomide) and a proteasome inhibitor
• PRIOR TO CELL PROCUREMENT: Received high dose melphalan followed by allogeneic stem cell transplantation (ASCT) or is not eligible for or has declined the procedure
• PRIOR TO CELL PROCUREMENT: Allogeneic stem cell transplantation is allowed provided the subject is >= 1 year from transplant, not on immunosuppressive therapy to treat/prevent graft-versus-host disease, has no evidence of active graft-versus-host disease, and has no evidence of active graft-versus-host disease or infection
• PRIOR TO CELL PROCUREMENT: Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded; WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year; the two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy; the male partner of WOCBP subjects enrolled into the trial should use a condom and female participants must take the responsibility to inform their partners of the need to use a condom
• PRIOR TO CELL PROCUREMENT: Not pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• PRIOR TO CELL PROCUREMENT: No tumor in a location where enlargement could cause airway obstruction
• PRIOR TO CELL PROCUREMENT: No diagnosis of any of the following conditions: amyloidosis, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin (POEMS) syndrome or multiple myeloma with central nervous system (CNS) involvement * Subjects with plasma cell leukemia are allowed to participate
• PRIOR TO CELL PROCUREMENT: No active inflammatory or infectious gastrointestinal disorder (e.g. infectious colitis, diverticulitis or inflammatory bowel disease)
• PRIOR TO CELL PROCUREMENT: No psychiatric illness which would prevent the subject from giving informed consent, or neurological illness that clinician believes would complicate monitoring for CNS neurotoxicity following CAR-T infusion
• PRIOR TO CELL PROCUREMENT: Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
• PRIOR TO CELL PROCUREMENT: No medical condition which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the subject
• PRIOR TO CELL PROCUREMENT: No other prior or concurrent malignancies with the exception of subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial at the investigator’s discretion
• PRIOR TO CELL PROCUREMENT: Adequate cardiac function, defined as: * No electrocardiography (ECG) evidence of acute ischemia * No ECG evidence of active, clinically significant conduction system abnormalities * Prior to study entry, any ECG abnormality at screening not felt to put the subject at risk must be documented by the investigator as not medically significant * No uncontrolled angina or severe ventricular arrhythmias * No clinically significant pericardial disease * No history of myocardial infarction within the last 6 months prior to registration * No class 3 or higher New York Heart Association congestive heart failure
• PRIOR TO CELL PROCUREMENT: No active infection (fungal, bacterial or viral) including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells); Note: to meet eligibility, subjects are required to be negative for HIV antibody or HIV viral load, negative for hepatitis B surface antigen, and negative for HCV antibody or HCV viral load
• PRIOR TO CELL PROCUREMENT: Calculated creatinine clearance >= 30 mL/min using the Cockcroft-Gault formula (chemistries to be completed within 7 days of procurement; complete blood count [CBC] with [w]/differential [diff] required within 24 hours of procurement)
• PRIOR TO CELL PROCUREMENT: Bilirubin =< 1.5 x upper limit of normal (ULN) unless attributed to Gilbert’s syndrome (chemistries to be completed within 7 days of procurement; CBC w/diff required within 24 hours of procurement)
• PRIOR TO CELL PROCUREMENT: Aspartate aminotransferase (AST) =< 2.5 x ULN (chemistries to be completed within 7 days of procurement; CBC w/diff required within 24 hours of procurement)
• PRIOR TO CELL PROCUREMENT: Alanine aminotransferase (ALT) =< 2.5 x ULN (chemistries to be completed within 7 days of procurement; CBC w/diff required within 24 hours of procurement)
• PRIOR TO CELL PROCUREMENT: Oxygen saturation >= 90% on room air
• PRIOR TO CELL PROCUREMENT: Ejection fraction >= 50%
• PRIOR TO CELL PROCUREMENT: Platelets >= 50 000 /mm^3 (50 x 10^9/L) within 60 days of cell procurement and >= 20,000/mm^3 (20 × 10^9/L) within 24 hours of procurement; subjects should not have received platelet transfusions within 1 week of screening (chemistries to be completed within 7 days of procurement; CBC w/diff required within 24 hours of procurement)
• PRIOR TO CELL PROCUREMENT: Absolute neutrophil count (ANC) >= 1000 /mm^3 (1.0 x 10^9/L) within 60 days of cell procurement and >= 500/mm^3 (0.5 × 10^9/L) within 24 hours of procurement; subjects should not have received granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 1 week or pegylated G-CSF (Neulasta) within 2 weeks of screening (chemistries to be completed within 7 days of procurement; CBC w/diff required within 24 hours of procurement)
• PRIOR TO CELL PROCUREMENT: Negative serum pregnancy test within 72 hours prior to procurement and again 72 hours prior to lymphodepleting therapy for female participants of child bearing potential; NOTE: females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• PRIOR TO CELL PROCUREMENT: Subjects who have received prior CAR-T must be >= 9 months out from prior CAR-T and have no available or more suitable treatment options in the opinion of the treating investigator
• PRIOR TO LYMPHODEPLETION: Written informed consent to enroll in the CAR T-cell therapy trial must be obtained prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Karnofsky score of >= 60%
• PRIOR TO LYMPHODEPLETION: Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded; WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year; the two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy; the male partner of WOCBP subjects enrolled into the trial should use a condom and female participants must take the responsibility to inform their partners of the need to use a condom
• PRIOR TO LYMPHODEPLETION: Not pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• PRIOR TO LYMPHODEPLETION: No tumor in a location where enlargement could cause airway obstruction
• PRIOR TO LYMPHODEPLETION: No diagnosis of any of the following conditions: amyloidosis, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome or multiple myeloma with central nervous system (CNS) involvement * Subjects with plasma cell leukemia are allowed to participate
• PRIOR TO LYMPHODEPLETION: No active inflammatory or infectious gastrointestinal disorder (e.g. infectious colitis, diverticulitis or inflammatory bowel disease)
• PRIOR TO LYMPHODEPLETION: No psychiatric illness which would prevent the subject from giving informed consent or neurological illness that clinician believes would complicate monitoring for CNS neurotoxicity following CAR-T infusion
• PRIOR TO LYMPHODEPLETION: Subject is willing and able to comply with study procedures based on the judgement of the investigator
• PRIOR TO LYMPHODEPLETION: No medical condition which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the subject
• PRIOR TO LYMPHODEPLETION: Subject is a good candidate for treatment with CAR138 T-cells per the investigator’s discretion.
• PRIOR TO LYMPHODEPLETION: No other prior or concomitant malignancies with the exception of subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial at the investigator’s discretion
• PRIOR TO LYMPHODEPLETION: Adequate cardiac function, defined as: • No ECG evidence of acute ischemia • No ECG evidence of active, clinically significant conduction system abnormalities • Prior to study entry, any ECG abnormality at screening not felt to put the subject at risk has to be documented by the investigator as not medically significant • No uncontrolled angina or severe ventricular arrhythmias • No clinically significant pericardial disease • No history of myocardial infarction within the last 6 months prior to registration • No class 3 or higher New York Heart Association congestive heart failure
• PRIOR TO LYMPHODEPLETION: No active infection (fungal, bacterial or viral) including HIV, HBV, HCV (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells); Note: to meet eligibility, subjects are required to be negative for HIV antibody or HIV viral load, negative for hepatitis B surface antigen, and negative for HCV antibody or HCV viral load
• PRIOR TO LYMPHODEPLETION: Subjects must have autologous transduced activated CAR138 T-cells that meet the Certificate of Analysis (CofA) acceptance criteria
• PRIOR TO LYMPHODEPLETION: Subjects must have stopped taking corticosteroids for at least 48 hours prior to lymphodepleting chemotherapy; (No current use of systemic corticosteroids at doses ≥10mg prednisone daily or its equivalent; those receiving < 10mg/day prednisone equivalent may be enrolled at discretion of the investigator)
• PRIOR TO LYMPHODEPLETION: Subjects must have stopped systemic chemotherapy at least 14 days prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subjects must have stopped radiation therapy at least 7 days prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Subjects should have repeat multiple myeloma serologies performed within 7 days of lymphodepletion; if markers of measurable disease no longer fall within the guidelines outlined, the principal investigator should be contacted; in such an event, the subject may be allowed to receive lymphodepletion and CAR138 T-cell infusion if it is felt to be in the subject’s best interests; the subject would not be evaluable for response (disease not measurable) but would be evaluable for all other safety and efficacy measures
• PRIOR TO LYMPHODEPLETION: Absolute neutrophil count (ANC) >= 1000 cells/mm^3 (1.0 x 10^9/L) (obtained within 72 hours prior to lymphodepletion); subjects should not have received G-CSF or GM-CSF within 1 week or pegylated G-CSF (Neulasta) within 2 weeks of screening for lymphodepletion
• PRIOR TO LYMPHODEPLETION: Platelets >= 50,000 cells/mm^3 (50 x 10^9/L) (obtained within 72 hours prior to lymphodepletion); subjects should not have received platelet transfusion within 1 week of screening for lymphodepletion
• PRIOR TO LYMPHODEPLETION: Calculated creatinine clearance >= 30 mL/min, using the Cockcroft-Gault formula (obtained within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Bilirubin =< 1.5 x ULN (obtained within 72 hours prior to lymphodepletion) unless attributed to Gilbert’s syndrome
• PRIOR TO LYMPHODEPLETION: Aspartate aminotransferase (AST) =< AST =< 2.5 x ULN (obtained within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Alanine aminotransferase (ALT) =< AST =< 2.5 x ULN (obtained within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Pulse oximetry >= 90% on room air (obtained within 72 hours prior to lymphodepletion)
• PRIOR TO LYMPHODEPLETION: Has not received treatment with any investigational drug within 21 days or any tumor vaccines within the previous six weeks prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: No major surgery within 28 days prior to lymphodepletion
• PRIOR TO LYMPHODEPLETION: Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) prior to lymphodepletion through 3 months after the last dose of study therapy
• PRIOR TO LYMPHODEPLETION: Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for female participants of childbearing potential; NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• PRIOR TO CAR138 T CELL INFUSION: Karnofsky score of >= 60%
• PRIOR TO CAR138 T CELL INFUSION: Women of childbearing potential (WOCBP) should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study, and for 6 months after the study is concluded; WOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year; the two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy; the male partner of WOCBP subjects enrolled into the trial should use a condom and female participants must take the responsibility to inform their partners of the need to use a condom
• PRIOR TO CAR138 T CELL INFUSION: No tumor in a location where enlargement could cause airway obstruction
• PRIOR TO CAR138 T CELL INFUSION: Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee
• PRIOR TO CAR138 T CELL INFUSION: No medical condition which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the subject
• PRIOR TO CAR138 T CELL INFUSION: No active infection (fungal, bacterial or viral)
• PRIOR TO CAR138 T CELL INFUSION: No neurological illness that clinician believes would complicate monitoring for CNS neurotoxicity following CAR-T infusion
• PRIOR TO CAR138 T CELL INFUSION: Bilirubin =<1.5 ULN unless attributed to Gilbert’s syndrome
• PRIOR TO CAR138 T CELL INFUSION: AST =< 5 times ULN
• PRIOR TO CAR138 T CELL INFUSION: ALT =< 5 times ULN
• PRIOR TO CAR138 T CELL INFUSION: Serum creatinine < 2 times ULN
• PRIOR TO CAR138 T CELL INFUSION: Pulse oximetry of > 90% on room air
• PRIOR TO CAR138 T CELL INFUSION: No current use of systemic corticosteroids at doses >= 10mg prednisone daily or its equivalent; those receiving < 10mg daily may be enrolled at discretion of the investigator
• PRIOR TO CAR138 T CELL INFUSION: Subject is a good candidate for treatment with CAR138 T-cells, in the opinion of the treating physician
• PRIOR TO CAR138 T CELL INFUSION: Subject has no clinical indication of rapidly progressing disease in the opinion of the treating physician