MM CAR-T to Upgrade Response BMTCTN1902

Inclusion Criteria:

   1. Age greater than or equal to 18.00 years

   2. Patients must meet the criteria for symptomatic MM requiring therapy (Appendix A)
   prior to initiating initial systemic anti-myeloma treatment.

   3. Patients must have received initial systemic anti- myeloma therapy consisting of
   induction therapy and consolidation with high-dose melphalan (>140 mg/m2 ) followed by
   an auto HCT (minimum cell dose of 2x106 CD34+ cells/kg (actual body weight) within 12
   months from initiation of systemic anti-myeloma therapy.

   4. Patient must have additional stored stem cells greater than or equal to 2x106 CD34+
   cells per kg actual body weight.

   5. Patients must be less than or equal to 12 months after autologous HCT at the time of
   enrollment.

   6. Patients must have initiated maintenance therapy with lenalidomide-based regimen
   within 6 months after the auto HCT and have received at least 3 months of maintenance
   prior to enrollment.

   7. Patients must have tolerated a minimum dose of lenalidomide 5 mg/day for 21 days of a
   28-day cycle for greater than 2 cycles without having to stop due to toxicities.

   8. Patients must have a VGPR or less (Section 3.1) in reference to time time of
   initiation of initial systemic anti-myeloma therapy at study enrollment.

   9. Patients must have Karnofsky performance greater than or equal to 70.

10. Patients must have recovered to Grade 1 or baseline of any non-hematologic toxicities
   due to prior treatments, excluding Grade 2 neuropathy.

11. Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 without filgrastim
   use in the prior 14 days.

12. Platelet count greater than 100,000/mm3 (without platelet transfusion in the previous
   7 days or thrombopoietin mimetics in the previous 28 days).

13. Hemoglobin greater than 9 g/dL (without red blood cell transfusion in the previous 7
   days).

14. Creatinine Clearance (CrCl) greater than or equal to 60 mL/min, measured or estimated
   by Cockcroft-Gault equation.

15. Corrected serum calcium less than or equal to 13.5 mg/dL.

16. Oxygen saturation greater than 92% on room air.

17. Hepatic Function: a. Serum aspartate aminotransferase (AST) and alanine
   aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) b.
   Serum total bilirubin less than or equal to 2 x ULN. Patients who have been diagnosed
   with Gilbert's disease are permitted to exceed the defined bilirubin value of 2 x ULN

18. International ratio (INR) or partial thromboplastin time (PTT) less than 1.5 x ULN

19. Cardiac Function: left ventricular ejection fraction greater than 45% by
   echocardiogram or MUGA.

20. Patients must be 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.

21. Female patients of childbearing potential (FCBP1 ) must: a. Have a negative serum
   pregnancy test with a sensitivity of at least 50 mIU/mL prior to enrollment b. Agree
   to use, and be able to comply with, TWO acceptable methods of birth control (Appendix
   C), one highly effective method and one additional effective (barrier) method AT THE
   SAME TIME, from screening through at least 1 year following bb2121 infusion or 4 weeks
   following discontinuation of lenalidomide, whichever is later. c. Agree to abstain
   from breastfeeding from screening through at least 1 year following bb2121 infusion or
   4 weeks following discontinuation of lenalidomide, whichever is later.

22. Male patients must: a. 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 bb2121 infusion or 4 weeks following discontinuation
   of lenalidomide whichever is later b. Must not donate sperm from screening through at
   least 1 year following bb2121 infusion or 4 weeks following discontinuation of
   lenalidomide whichever is later.

Exclusion Criteria:

   1. Patients with a prior allogeneic hematopoietic cell.

   2. Female of childbearing potential (FCBP) is a female who:

      - has achieved menarche at some point,

      - has not undergone a hysterectomy or bilateral oophorectomy or

      - has not been naturally postmenopausal (amenorrhea following cancer therapy does
      not rule out childbearing potential) for at least 24 consecutive months (i.e.,
      has had menses at any time in the preceding 24 consecutive months).

   3. Patients with disease progression (see Section 3.1.2 for disease progression
   definition) at any time prior to enrollment.

   4. Patients receiving any of the following less than 14 days prior to enrollment:

      1. Plasmapheresis

      2. Major surgery (as defined by the investigator)

      3. Radiation therapy other than local therapy for MM-associated bone lesions

      4. Use of any systemic anti-myeloma drug therapy (with the exception of lenalidomide
      maintenance)

      5. Any investigational agents

      6. Corticosteroids (Physiologic replacement, topical, intranasal and inhaled
      steroids are permitted)

   5. Patients with known Central Nervous System (CNS) involvement with MM.

   6. Patients with a prior organ transplant requiring systemic immunosuppressive therapy.

   7. Patients who previously experienced toxicities related to lenalidomide resulting in
   permanent treatment discontinuation.

   8. Patients who experienced thromboembolic events while on full anticoagulation during
   prior therapy with an immunomodulatory agent (IMiD).

   9. Patients unwilling to take DVT prophylaxis while on lenalidomide maintenance.

10. Patients with history of greater than or equal to Grade 2 hemorrhage within 30 days of
   enrollment.

11. Patient requiring ongoing treatment with chronic, therapeutic dosing of anticoagulants
   (e.g. Warfarin, low molecular weight heparin, Factor Xa inhibitors).

12. Patients with 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.

13. Patients with active or history of plasma cell leukemia, Waldenstrom's
   macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal
   protein, and skin changes), or clinically significant amyloidosis.

14. Patients with purely non-secretory MM [prior to starting systemic therapy, absence of
   a monoclonal protein (M protein) in serum as measured by electrophoresis and
   immunofixation and the absence of Bence Jones protein in the urine defined by use of
   conventional electrophoresis and immunofixation techniques and the absence of involved
   serum free light chain greater than 100mg/L]. Patients with light chain MM detected in
   the serum by free light chain assay are eligible.

15. Patients with a 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 starting study treatment.

16. Patients with ongoing treatment with chronic immunosuppressants (e.g. cyclosporine or
   systemic steroids at any dose). Physiologic replacement, intermittent topical, inhaled
   or intranasal corticosteroids are allowed.

17. Patients with 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.

18. Patients 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.

19. Patients with previous history of treatment with any gene therapy-based therapeutic
   for cancer or investigational cellular therapy for cancer or BCMA targeted therapy.

20. Patients with 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 Protocol Officer or one of the
   Protocol Chairs. Cancer treated with curative intent greater than 5 years prior to
   enrollment is allowed.

21. Female patients who are pregnant (positive beta-HCG), or breastfeeding, or who intend
   to become pregnant during participation in the study.

22. Patient with known allergy or hypersensitivity to any of the study medications, their
   analogues, or excipients in the various formulations of any agent.

23. Patient with serious medical of psychiatric illness likely to interfere with
   participation on this clinical study.

24. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
   medication and with progression or no clinical improvement) at time of enrollment.

25. Patients unwilling or unable to provide informed consent 25. Patients unable or
   unwilling to return to the transplant center for treatment and follow up.