A Phase 3, Multicenter, Randomized, Open Label Study to Compare the Efficacy and Safety of BB2121 Versus Standard Regimens in Subjects with Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3)
- Conditions
- Relapsed and Refractory Multiple MyelomaCancer of the bone marrow that recurs or is resistant to treatment1003522710018865
- Registration Number
- NL-OMON56296
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 16
1. Subject is >= 18 years of age at the time of signing the informed consent
form (ICF)
2. Subject must understand and voluntarily sign an ICF prior to any
study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other
protocol requirements within this protocol and for a subject randomized to
Treatment Arm A, subject agrees to continued follow-up for up to 15 years as
mandated by the regulatory guidelines for gene therapy trials.
4. Subject has documented diagnosis of MM and measurable disease, defined as:
• M-protein (serum protein electrophoresis [sPEP] or urine protein
electrophoresis [uPEP]): sPEP >= 0.5 g/dL or uPEP >= 200 mg/24 hours and/or
• Light chain MM without measurable disease in the serum or urine: Serum
immunoglobulin free light chain >= 10 mg/dL and abnormal serum immunoglobulin
kappa lambda free light chain ratio
5. Subject has received at least 2 but no greater than 4 prior MM regimens.
Note: induction with or without hematopoietic stem cell transplant and with or
without maintenance therapy is considered as one regimen.
6. Subject has received prior treatment with DARA, a proteasome inhibitor- and
an immunomodulatory compound-containing regimen for at least 2 consecutive
cycles.
7. Subject must be refractory to the last treatment regimen. Refractory is
defined as documented progressive disease during or within 60 days (measured
from the last dose of any drug within the regimen) of completing treatment with
the last anti-myeloma regimen before study entry.
8. Subject achieved a response (minimal response [MR] or better) to at least 1
prior treatment regimen.
9. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1.
10. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to
prior treatments, excluding alopecia and Grade 2 peripheral neuropathy.
11. Adequate vascular access for leukapheresis.
12 and 13. Adequate contraceptive measures as outlined in the protocol.
Refer to protocol for additional inclusion criteria.
1. Subject has any significant medical condition, laboratory abnormality, or
psychiatric illness that would prevent the subject from participating in the
study. 2. Subject has any condition including the presence of laboratory
abnormalities, which places the subject at unacceptable risk if he/she were to
participate in the study. 3. Subject has any condition that confounds the
ability to interpret data from the study. 4. Subject has nonsecretory MM. 5.
Subject has any of the following laboratory abnormalities: a. Absolute
neutrophil count (ANC) < 1,000/µL b. Platelet count: < 75,000/µL in
subjects in whom < 50% of bone marrow nucleated cells are plasma cells and
platelet count < 50,000/µL in subjects in whom >= 50% of bone marrow
nucleated cells are plasma cells (it is not permissible to transfuse a subject
to reach this level) c. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not
permissible to transfuse a subject to reach this level) d. Serum creatinine
clearance (CrCl) < 45 mL/min e. Corrected serum calcium > 13.5 mg/dL
(> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) > 2.5 × upper limit of normal (ULN) g. Serum total
bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented
Gilbert*s syndrome h. International normalized ratio (INR) or activated partial
thromboplastin time (aPTT) > 1.5 × ULN, or history of Grade >= 2 hemorrhage
within 30 days, or subject requires ongoing treatment with chronic, therapeutic
dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa
inhibitors) 6. Subject has inadequate pulmonary function defined as oxygen
saturation (SaO2) < 92% on room air. 7. Subject has prior history of
malignancies, other than MM, unless the subject has been free of the disease
for >= 5 years with the exception of the following non-invasive malignancies: •
Basal cell carcinoma of the skin • Squamous cell carcinoma of the skin •
Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental
histologic finding of prostate cancer (T1a or T1b using the tumor, nodes,
metastasis [TNM] clinical staging system) or prostate cancer that can be
treated with curative intent 8. Subject has active or history of plasma cell
leukemia, Waldenstrom*s macroglobulinemia, POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes) or
amyloidosis. 9. Subject with known central nervous system (CNS) involvement
with myeloma. 10. Subject has clinical evidence of pulmonary leukostasis and
disseminated intravascular coagulation. 11. Subject has known chronic
obstructive pulmonary disease (COPD) with a forced expiratory volume in 1
second (FEV1) 50% of predicted normal. Note that forced expiratory testing
(FEV1) is required for subjects suspected of having COPD and subjects must be
excluded if FEV1 is < 50% of predicted normal. 12. Subject has a 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. Subject was treated with DARA in combination
with POM with or without dexamethasone (DP±d) as part of their most r
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression-free Survival (PFS): Time from randomization to the first<br /><br>documentation of progressive disease based on the International Myeloma Working<br /><br>Group (IMWG) Uniform Response Criteria for Multiple Myeloma (Kumar, 2016)<br /><br>assessed by an independent response committee (IRC) or death due to any cause </p><br>
- Secondary Outcome Measures
Name Time Method