A study to assess the 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 MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10067095Term: Multiple myeloma progressionSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002245-29-IT
- Lead Sponsor
- CELGENE CORPORATIO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 140
For updates please refer to section of updated Protocol. Eligibility is determined prior to leukapheresis. Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is = 18 years of age at the time of signing the informed consent form (ICF).
2. Documented diagnosis of multiple myeloma
- Must have received at least 3 prior MM treatment regimens. Note:induction with or without hematopoietic stem cell transplant and with or
without maintenance therapy is considered a single regimen.
- Must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen.
- Must have received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.
- 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 completing treatment with the last anti-myeloma drug regimen before study entry.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
4. Subjects must have measurable disease, including at least one of the criteria below:
- Serum M-protein greater or equal to 1.0 g/dL
- Urine M-protein greater or equal to 200 mg/24 h
- Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal
- Bone marrow plasma cells > 30% of total bone marrow cells
5. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy.
6. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
7. Subject is willing and able to adhere to the study visit schedule and other protocol requirements within this protocol as well as agrees to continued follow-up for up to 15 years as mandated by the regulatory
guidelines for gene therapy trials.
8. Females of childbearing potential (FCBP (see note 1 below)) 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, effective measures of contraception without interruption, from screening through at least 1 year following lymphodepleting chemotherapy. ref to Protocol
- Agree to abstain from breastfeeding during study participation. There are insufficient exposure data to provide any recommendation concerning the total duration of abstaining from breastfeeding following treatment with bb2121. Ref to Protocol
- Refrain from tissue donation including egg donation or any other tissue/blood/organ donations for at least 1 year following lymphodepleting chemotherapy. There are insufficient exposure data to provide any recommendation concerning the duration of refraining from tissue donation following treatment with bb2121. Ref to protocol
Note 1: A female of childbearing potential is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 2
Please refers to the specific Protocol updates Section. The presence of any of the following will exclude a subject from enrollment:
1. Subjects with known central nervous system involvement with myeloma.
2. History or presence of clinically relevant central nervous system (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: this criterion does not apply to subjects
undergoing retreatment unless Grade 4 neurotoxicity was observed following prior treatment with bb2121).
3. Subjects with plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis.
4. Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease.
5. Inadequate hepatic function defined by AST and/or ALT > 2.5 × upper limit of normal (ULN) and total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome and direct bilirubin is = 1.5 x ULN).
6. Inadequate renal function defined by CrCl = 45 ml/min using Cockcroft-Gault equation.
7. 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, or Factor Xa inhibitors).
8. Inadequate bone marrow function defined by absolute neutrophil count (ANC) < 1000 cells/mm3 in the absence of growth factor support (filgrastim within 7 days or peg-filgrastim within 14 days of screening) and platelet count < 50,000 mm3 in the absence of transfusion support (platelet transfusion within 7 days of screening).
9. Echocardiogram or MUGA with left ventricular ejection fraction < 45%.
10. Inadequate pulmonary function as defined as oxygen saturation (Sa02) < 92 % on room air.
11. Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed.
12. 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.
13. Evidence of human immunodeficiency virus (HIV) infection.
14. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
- Subjects who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA negative are eligible
- Subjects who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible
- Subjects who are seropositive because of hepatitis B virus vaccine are eligible
- Subjects with known HBV infection should have undetectable HBV viral load and be maintained on anti-viral therapy to prevent HBV reactivation.
15. Seropositive for and with active viral infection with hepatitis C virus (HCV)
- Subjects who had hepatitis C but have received an antiviral treatment and show no detectable HCV viral RNA for 6 months are eligible.
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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