A study to assess the efficacy and safety of bb2121 in people who have Myeloma that is not responsive after treatment or who had Myeloma which has returned after a period of treatment.
- Conditions
- Relapsed and Refractory Multiple Myeloma and High-Risk Multiple Myeloma Having Progressed Within One Year of Initial TreatmentMedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851MedDRA version: 20.0 Level: LLT Classification code 10067095 Term: Multiple myeloma progression System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000264-28-FR
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 122
1. Subject is = 18 years of age at the time of signing the informed consent form (ICF)
2. Subject has 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
3. Subjects with one of the following cohort specific requirements:
Cohort 1 RRMM subjects with = 3 prior anti-myeloma treatment regimens:
• Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
• Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
• Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
• Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
• Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen
Cohort 2 HR and with 1 prior anti-myeloma treatment regimen:
• Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
• Subject must have the following HR factors:
- R-ISS stage III
AND
- Early relapse defined as:
- For subjects that have undergone transplant, PD < 12 months since date of first transplant
- For subjects that have received only induction, PD < 12 months since date of last treatment regimen which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone
4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status = 1
5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy
6. Subject must have adequate vascular access for leukapheresis
7. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
8. Subject is willing and able to adhere to the study visit schedule and other protocol requirements as well as agrees to continued follow up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials
9. Female subjects of childbearing potential (FCBP) must:
• Have a negative pregnancy test as verified by the Investigator, one negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test result at screening, prior to LD chemotherapy. This applies even if the subject practices true abstinence* from heterosexual contact
• Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effectiv
1. Subject used any investigational agents within 28 days of leukapheresis
2. Subject received any of the following within the last 14 days of leukapheresis:
a. Plasmapheresis
b. Major surgery (as defined by the investigator)
c. Radiation therapy other than local therapy for myeloma associated bone lesions
d. Use of any systemic anti-myeloma drug therapy
3. Subject with known CNS involvement with myeloma
4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
5. 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. (Note: Only if subject experienced Grade 4 neurotoxicity following bb2121 treatment is this exclusion criteria applicable before retreatment with bb2121 (Cohort 1)
6. Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis
7. Subject has nonsecretory MM
8. Subject has any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) < 1,000/µL
b. Platelet count < 50,000 mm3 in the absence of transfusion support (platelet transfusion within 7 days of screening)
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 ratio (INR) or partial thromboplastin time (PTT) > 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)
9. Echocardiogram (ECHO) or multi-gated acquisition (MUGA) with left ventricular ejection fraction < 45%
10. Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
11. Inadequate pulmonary function defined as oxygen saturation (Sa02) < 92 % on room air
12. Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed
13. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy
14. Subject has received ASCT within 12 weeks prior to l
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method