A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM)

Inclusion Criteria:

Subjects must satisfy all of the following criteria to be enrolled in the study:

Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
Subject is ≥ 18 years of age at the time of initial diagnosis of MM

Subject has measurable disease at initial diagnosis by

M-protein and/or
Light chain MM without measurable disease in the serum or urine

Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG:

ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or;
ISS Stage III and serum LDH > ULN
Subject has Eastern Cooperative Oncology Group performance ≤ 1

Subjects has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment:

Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd)
Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment: The presence of any of the following will exclude a subject from enrollment:

At initial diagnosis, screening and prior to initiation of induction therapy for MM:

Subject has non-secretory MM

During Screening:

Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol

Subject has any of the following laboratory abnormalities:

Absolute neutrophil count < 1,000/μL
Platelet count < 50,000 mm3
Hemoglobin < 8 g/dL (< 4.9 mmol/L)
Serum creatinine clearance < 45 mL/min
Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal
Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
INR or aPTT > 1.5 × ULN
Subject has history or presence of clinically significant CNS pathology
Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy
Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen
Subjects has moderate or severe pulmonary hypertension
Subject has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug
Subject has not recovered from induction therapy-related toxicities (non-hematologic) to < grade 1 CTCAE at the time of screening
Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment

Subject has cardiac conditions such as:

Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction < 45%
Subject has a history of clinically significant cardiovascular disease or clinically significant ECG abnormalities

Subject has Pulmonary conditions such as:

Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal.
Inadequate pulmonary function defined as oxygen saturation < 92 % on room air
Subject needs ongoing treatment with chronic immunosuppressants
Subject has history of primary immunodeficiency
Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C