Note: The following eligibility criteria are divided into 3 sections: 1) eligibility
criteria to be fulfilled prior to cell procurement, (section 3.1); 2) eligibility criteria
to be met prior to lymphodepletion (section 3.2); and 3) eligibility criteria to be met
prior to CAR138 T cell infusion (section 3.3).
Note: During the period of cell procurement and CAR138 T-cell production, patients are
allowed to receive additional standard of care chemotherapy or radiation therapy to
stabilize their multiple myeloma if the treating physician feels it is in the patient's
best interests. For subjects requiring bridging chemotherapy and/or radiation therapy while
awaiting manufacture of their CAR138-T cells, details regarding treatment(s) administered
including doses, frequency, number of cycles, etc. will be collected.
Eligibility criteria to be fulfilled prior to cell procurement
Patients must fulfill all of the following criteria to participate in this study.
Written informed consent and HIPAA authorization for release of personal health
information. Patients must sign a consent to undergo cell procurement.
Age ≥ 18 years at the time of consent.
Karnofsky score of ≥ 60%.
Diagnosis of relapsed or refractory multiple myeloma (as defined by the Revised Uniform
Response Criteria outlined by the IMWG
Measurable disease as defined by one or more of the following: 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.
Patients with non-secretory disease and a baseline marrow burden of myeloma of at least 30%
will also be eligible to participate.
Received at least 3 lines of prior chemotherapy. The prior regimens must have included an
immunomodulatory agent (lenalidomide or pomalidomide) and a proteasome inhibitor
(bortezomib, carfilzomib or ixazomib).
- Two lines of therapy will be allowed if the patient has disease that is refractory to
both an immunomodulatory agent (lenalidomide or pomalidomide) and a proteasome
inhibitor.
Received high dose melphalan followed by autologous stem-cell transplant (ASCT) or is not
eligible for or has declined the procedure.
Allogeneic stem cell transplantation is allowed provided the patient is ≥ 1 year from
immunosuppressive therapy to treat/prevent graft-versus-host disease, has no evidence of
active graft-versus-host disease, and has no evidence of active infection.
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
(starting prior to procurement), 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 patients
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.
Not pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
No tumor in a location where enlargement could cause airway obstruction.
No diagnosis of any of the following conditions: amyloidosis, POEMS syndrome or multiple
myeloma with CNS involvement.
- Patients with plasma cell leukemia are allowed to participate.
No active inflammatory or infectious gastrointestinal disorder (e.g. infectious colitis,
diverticulitis or inflammatory bowel disease).
No psychiatric illness which would prevent the patient from giving informed consent, or
neurological illness that clinician believes would complicate monitoring for CNS
neurotoxicity following CAR-T infusion.
Subjects is willing and able to comply with study procedures based on the judgement of the
investigator or protocol designee.
No medical condition, which, in the opinion of the treating physician, would make this
protocol unreasonably hazardous for the patient.
No other prior or concomitant malignancies with the exception of:
- Non-melanoma skin cancer
- In-situ malignancy
- Low-risk prostate cancer after curative therapy
- Other cancer for which the patient has been disease free for ≥ 3 years.
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 patient 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
No active infection (fungal, bacterial or viral) including HIV, HTLV, 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, patients
are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2
antibody or PCR negative for HTLV1 and 2, negative for Hepatitis B surface antigen, and
negative for HCV antibody or HCV viral load.
Demonstrate adequate organ function prior to cell procurement as defined below:
- Creatinine Clearance using the Cockcroft-Gault formula: ≥ 50 mL/min
- Bilirubin: ≤ 1.5 × upper limit of normal (ULN) unless attributed to Gilbert's syndrome
- Aspartate aminotransferase (AST): ≤ 2.5 × ULN
- Alanine aminotransferase (ALT): ≤ 2.5 × ULN
- Oxygen saturation: ≥ 92% on room air
- Ejection fraction: ≥ 50%
- Hemoglobin: ≥ 8.0 g/dL; transfusion of red blood cells within 1 weeks will be
permitted
- Platelets: ≥ 50,000 /mm^3; Patients should not have received platelet transfusions
within 1 week of screening
- ANC: ≥ 1000 /mm^3; Patients 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
Negative serum pregnancy test within 72 hours prior to cell procurement 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.
Eligibility Criteria to be fulfilled prior to lymphodepletion
__________________________________________________ Written informed consent to enroll in
the CAR T-cell therapy trial must be obtained prior to lymphodepletion.
Karnofsky score of ≥ 60%.
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
(starting prior to procurement), 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 patients
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.
Not pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
No tumor in a location where enlargement could cause airway obstruction.
No diagnosis of any of the following conditions: amyloidosis, POEMS syndrome or multiple
myeloma with CNS involvement.
- Patients with plasma cell leukemia are allowed to participate.
No active inflammatory or infectious gastrointestinal disorder (e.g. infectious colitis,
diverticulitis or inflammatory bowel disease).
No psychiatric illness which would prevent the patient from giving informed consent or
neurological illness that clinician believes would complicate monitoring for CNS
neurotoxicity following CAR-T infusion
Subjects is willing and able to comply with study procedures based on the judgement of the
investigator or protocol designee.
No medical condition, which, in the opinion of the treating physician, would make this
protocol unreasonably hazardous for the patient.
Subject is a good candidate for treatment with CAR138 T-cells per the investigator's
discretion.
No other prior or concomitant malignancies with the exception of:
- Non-melanoma skin cancer
- In-situ malignancy
- Low-risk prostate cancer after curative therapy
- Other cancer for which the patient has been disease free for ≥ 3 years.
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 patient 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
No active infection (fungal, bacterial or viral) including HIV, HTLV, 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, patients
are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2
antibody or PCR negative for HTLV1 and 2, negative for Hepatitis B surface antigen, and
negative for HCV antibody or HCV viral load.
Patients must have autologous transduced activated CAR138 T-cells that meet the Certificate
of Analysis (CofA) acceptance criteria.
Patients must have stopped taking corticosteroids for at least 48 hours prior to
lymphodepleting chemotherapy; (those receiving <10mg/day prednisone equivalent may be
enrolled at discretion of the Investigator)
Patients must have stopped systemic chemotherapy for at least 14 days prior to
lymphodepletion
Patients must have stopped radiation therapy for at least 7 days prior to lymphodepletion
Patients should have repeat multiple myeloma serologies performed within 7 days of
lymphodepletion. If markers of measurable disease no longer fall within the guidelines
outlined above (procurement eligibility criterion #5), the Principal Investigator should be
contacted. In such an event, the patient may be allowed to receive lymphodepletion and
CAR138 T-cell infusion if it is felt to be in the patient's best interests. The patient
would not be evaluable for response (disease not measurable) but would be evaluable for all
other safety and efficacy measures.
Patients must demonstrate adequate organ function prior to lymphodepletion as defined
below; all tests must be obtained within 72 hours prior to lymphodepletion.
- Hemoglobin: ≥ 8 g/dL
- Absolute Neutrophil Count (ANC): ≥ 1000 cells/mm^3; patients should not have received
G-CSF or GM-CSF within 1 week or pegylated G-CSF (Neulasta) within 2 weeks of
screening for lymphodepletion
- Platelets: ≥ 50,000 cells/mm^3; patients should not have received platelet transfusion
within 1 week of screening for lymphodepletion
- Calculated creatinine clearance: ≥ 50 mL/min using the Cockcroft-Gault formula
- Bilirubin: ≤ 1.5 × upper limit of normal (ULN) unless attributed to Gilbert's syndrome
- Aspartate aminotransferase (AST): ≤ AST ≤ 2.5 × ULN
- Alanine aminotransferase (ALT): ≤ AST ≤ 2.5 × ULN
- Pulse oximetry: ≥92% on room air
Has not received treatment with any investigational drug within 21 days or any tumor
vaccines within the previous six weeks prior to lymphodepletion.
No major surgery within 28 days prior to lymphodepletion.
Male patients 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.
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.
Eligibility Criteria to be fulfilled prior to CAR138 T-cell infusion
_______________________________________________________ Karnofsky score of ≥ 60%.
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
(starting prior to procurement), 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 patients
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.
No tumor in a location where enlargement could cause airway obstruction.
Subject is willing and able to comply with study procedures based on the judgement of the
investigator or protocol designee.
No medical condition which, in the opinion of the treating physician, would make this
protocol unreasonably hazardous for the patient.
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 patient at
risk has to be documented by the Investigator as not clinically 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
No active infection (fungal, bacterial or viral)
No neurological illness that clinician believes would complicate monitoring for CNS
neurotoxicity following CAR-T infusion
Evidence of adequate organ function as defined by:
- Bilirubin ≤1.5 times the upper limit of normal (ULN) unless attributed to Gilbert's
Syndrome
- AST ≤ 5 times ULN
- ALT ≤ 5 times ULN
- Serum creatinine ≤1.5 time ULN
- Pulse oximetry of > 90% on room air
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.
Subject is a good candidate for treatment with CAR138 T-cells.
Subject has no clinical indication of rapidly progressing disease in the opinion of the
treating physician.
