| Eligibility |
Inclusion Criteria:
Cohort 1:
- Patient with myeloma who has received at least four prior lines of treatment having
been exposed to an IMID, PI, and a CD38 monoclonal antibody and had measurable disease
prior to salvage high dose melphalan autoHCT done within the prior 2 - 6 months.
(Salvage melphalan/AutoHCT can count as the 4th line of treatment).
- Measurable disease is defined by any of the following:
- M-spike = 0.5mg/dL
- Urine m-spike = 200mg/dL/24 hours
- Involved Serum Free light chain = 10mg/dL
- Measurable plasmacytoma on imaging (= 1 lesion that has a single diameter = 2
cm).
- Bone marrow plasma cells = 30% as determined by CD138 immunohistochemistry
staining
Cohort 2:
- Patients with pathologically confirmed MM who have received at least 4 prior lines of
treatment having been exposed to an IMID, PI, and a CD38 monoclonal antibody and have
undergone an allo HCT for RRMM at any time in their history and have at least minimal
residual disease by flow or NGS in the bone marrow at least 3 months after allo HCT.
- Prior to Leukapheresis:
- Greater than age 18.
- Karnofsky performance = 70.
- Recovered to Grade 1 or baseline of any non-hematologic toxicities due to prior
treatments, excluding Grade 2 neuropathy
- Not receive any systemic anti-myeloma therapy for 14 days prior to leukapheresis.
Therapeutic doses of corticosteroids (defined as greater than 10 mg/day
prednisone or equivalent) are permitted until within 72 hours prior to
Leukapheresis.
- Absolute neutrophil count (ANC) = 1,000/mm^3 without filgrastim use in the prior
14 days.
- Hemoglobin = 8 g/dL (without red blood cell transfusion in the previous 7 days)
- Creatinine Clearance (CrCl) = 45 mL/min, measured or estimated by Cockcroft-Gault
equation.
- Corrected serum calcium = 13.5 mg/dL
- Oxygen saturation = 92% on room air
- Hepatic Function:
- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 x
upper limit of normal (ULN
- Serum total bilirubin Serum total bilirubin = 2 x ULN. Patients who have been
diagnosed with Gilbert's disease are permitted to exceed the defined bilirubin
value of 2 x ULN 2 x ULN. Patients who have been diagnosed with Gilbert's disease
are permitted to exceed the defined bilirubin value of 2 x ULN
- International ratio (INR) or partial thromboplastin time (PTT) = 1.5 x ULN
- Cardiac Function: left ventricular ejection fraction = 45% by echocardiogram
(ECHO) or multigated acquisition scan (MUGA).
- Willing and able to adhere to the study visit schedule and other protocol
requirements including regulatory requirement of a 15 year follow up using the
CIBMTR long term follow up mechanism.
- Female patients of childbearing potential (FCBP) must:
- Have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL
prior to enrollment
- Agree to use, and be able to comply with, TWO acceptable methods of birth
control, one highly effective method and one additional effective (barrier)
method AT THE SAME TIME, from screening through at least 1 year following Ide-Cel
infusion
- Agree to abstain from breastfeeding from screening through at least 1 year
following Ide-Cel infusion
- Male patients must:
- Agree to use a condom during sexual contact with a pregnant female or a FCBP,
even if he has undergone a successful vasectomy, from screening through at least
1 year following Ide-Cel infusion
- Must not donate sperm from screening through at least 1 year following Ide-Cel
infusion
- Prior to LD Chemotherapy
- Females of childbearing potential must have a negative serum pregnancy test = 7
days prior to LD chemotherapy
- Platelet count = 50,000/mm^3 (transfusion allowed)
- ANC = 1,000/mm^3 (without filgrastim within 72 hours)
- Hepatic Function:
- Serum AST and ALT = 2.5 × ULN
- Serum total bilirubin = 2 × ULN. Patients who have been diagnosed with Gilbert's
disease are permitted to exceed the defined bilirubin value of 2 x ULN
- CrCl = 45 mL/min, measured or estimated by Cockcroft-Gault equation
- INR or PTT = 1.5 x ULN
- No history of = Grade 2 hemorrhage within 30 days
- No presence of active/uncontrolled infection requiring systemic therapy. Prophylactic
antimicrobials are allowed.
- No intercurrent illness or toxicity that would place the subject at undue risk of
proceeding to LD chemotherapy
- Must not be taking therapeutic doses of corticosteroids (defined as greater than 10
mg/day prednisone or equivalent) within 72 hours prior to LD chemotherapy. Physiologic
replacement, topical, intranasal and inhaled steroids are permitted. Patients on
calcineurin inhibitors (cyclosporine or tacrolimus) should have levels considered
undetectable per institutional criteria
- No active urinary outflow obstruction
- Availability of manufactured cells
- Patients not meeting these criteria may still be eligible to initiate LD chemotherapy
with the approval of the Protocol PI (Principal Investigator).
- Prior to Ide-Cel or Cilta-Cel infusion
- Subjects who meet at least one of the following criteria on the day of scheduled CAR T
cell infusion should have its administration delayed:
- Suspected or active systemic infection
- Onset of fever = 38°C
- Requirement for supplemental oxygen to keep saturation greater than 91%
- Cardiac arrhythmia not controlled with medical management
- Hypotension requiring vasopressor support
- New onset or worsening of other non-hematologic organ dysfunction = Grade 3
- Taking any of the prohibited medications as described in Section 15
- Significant worsening in clinical status compared to initial eligibility criteria
that would, in the opinion of the treating physician, increase the risk of
adverse events associated with Ide-Cel or Cilta-Cel infusion.
Exclusion Criteria:
- Receiving any of the following less than 14 days prior to enrollment:
- Plasmapheresis
- Major surgery (as defined by the investigator)
- Radiation therapy other than local therapy for MM-associated bone lesions
- Prior organ transplant requiring systemic immunosuppressive therapy
- History of = Grade 2 hemorrhage within 30 days of enrollment
- Patient requiring ongoing treatment with chronic, therapeutic dosing of anticoagulants
(e.g., Warfarin, low molecular weight heparin, Factor Xa inhibitors) can be enrolled
with approval of the PI.
- History or presence of clinically relevant CNS pathology such as epilepsy, seizure,
paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain
injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,
or psychosis
- Having concurrent Waldenstrom's macroglobulinemia, POEMS (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically
significant amyloidosis
- History of Class III or IV congestive heart failure (CHF) or severe nonischemic
cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or
hemodynamically significant ventricular arrhythmia within the previous 6 months prior
to enrollment
- Active clinically significant autoimmune disease, defined as a history of requiring
systemic immunosuppressive therapy and at ongoing risk for potential disease
exacerbation. Patients with a history of autoimmune thyroid disease, asthma, or
limited skin manifestations are potentially eligible. Patients with a history of acute
or chronic GVHD are potentially eligible if on minimal immunosuppressants as defined
previously.
- Seropositive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B
or C, or acute hepatitis A. If any history of exposure to hepatitis B or C, then DNA
PCR should be negative. If hepatitis B core Ab positive with negative DNA PCR,
patients should be on prophylaxis while on study.
- Prior malignancies except resected basal cell carcinoma or treated carcinoma in situ.
Cancer treated with curative intent less than 5 years prior to enrollment will not be
allowed unless approved by the PI. Cancer treated with curative intent greater than 5
years prior to enrollment is allowed.
- Female patients who are breastfeeding or who intend to become pregnant during
participation in the study.
- Known allergy or hypersensitivity to any of the study medications, their analogues, or
excipients in the various formulations of any agent.
- Serious medical of psychiatric illness likely to interfere with participation on this
clinical study
- Uncontrolled bacterial, viral or fungal infections (currently taking medication and
with progression or no clinical improvement) at time of enrollment.
- Unwilling or unable to provide informed consent
- Unable or unwilling to return to the center for treatment and follow up
- No systemic anti-myeloma therapy is allowed within 7 days prior to leukapheresis.
Steroids are allowed, but should be tapered off by 72 hours prior to leukapheresis.
- Steroids are allowed between leukapheresis and LD chemotherapy, but should be tapered
off by 72 hours prior to lymphodepletion.
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