Multiple Myeloma Clinical Trial
A Study of Whether Ide-cel (bb2121) Can Be Made From People With Multiple Myeloma Who Have Had a Hematopoietic Cell Transplant
The purpose of this study is to see if the quality of T cells used to create ide-cel (bb2121) affects how ide-cel prevents cancer from coming back in people with relapsed or refractory multiple myeloma (MM), and who have had a hematopoietic cell transplant.
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
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
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)
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.
Receiving any of the following less than 14 days prior to enrollment:
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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There is 1 Location for this study
New York New York, 10065, United States More Info
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