A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Newly diagnosed multiple myeloma, BB2121, KarMMa-4, Phase I, NDMM, High Risk, R-ISS III, KRd, RVd, Dara-KRd, Dara-RVd, CyBorD, BCMA
Eligibility Criteria
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
Sites / Locations
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Arms of the Study
Arm 1
Experimental
Dose Escalation
bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10^6 CAR+ T cells. Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later