Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma

JRCT ID: jRCT1080224134

Registered date:06/11/2018

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Relapsed and Refractory Multiple Myeloma
• Date of first enrollment: 26/04/2019
• Target sample size: 12
• Countries of recruitment: Japan,North America,Europe
• Study type: Interventional

Intervention(s)

Investigational material(s)
Generic name etc: bb2121
INN of investigational material: idecabtagene vicleucel
Therapeutic category code: 429 Other antitumor agents
Dosage and Administration for Investigational material: Subjects will receive three days of fludarabine intravenously (30 mg/m2) and cyclophosphamide (300 mg/m2) for LD chemotherapy followed by 2 days of rest and bb2121 infusion at a dose ranging from 150 - 450 x 10^6 CAR+ T cells.

Control material(s)
Generic name etc: -
INN of investigational material: -
Therapeutic category code: -
Dosage and Administration for Investigational material:

Outcome(s)

Primary Outcome

Efficacy
- Overall Response Rate (ORR)

Secondary Outcome

Safety
Efficacy
Other
- Complete Response (CR) Rate
- Time to Response
- Duration of Response (DOR)
- Progression-free Survival (PFS)
- Time to Progression (TTP)
etc.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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.
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
5. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy.

Exclude criteria

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 active or history of 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 x upper limit of normal (ULN) and total bilirubin > 1.5 x 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 x ULN, or history of Grade >=2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anti-coagulants (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 pegfilgrastim 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 nondetectable 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.
16. Subjects 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.
17. Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, carcinoma in situ of the cervix, carcinoma in situ of the breast, or incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor nodes, metastasis clinical staging system]) or prostate cancer that is curative.
18. Subjects who are pregnant, or who intend to become pregnant during participation in the study.
19. Subject with known hypersensitivity to any component of bb2121 product (including the human serum, human serum albumin, fetal bovine serum, ingredients of murine origin and dimethyl sulfoxide (DMSO) that are used in the manufacture of the product), cyclophosphamide, fludarabine or tocilizumab.
20. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
21. 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. This includes systemic fungal, bacterial, viral, or other infection that is uncontrolled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antimicrobial treatment) or requiring IV antimicrobials for management.
22. Subject has any condition that confounds the ability to interpret data from the study.

Related Information

• Primary Sponsor: Bristol-Myers Squibb K.K.
• Secondary ID(s): NCT03361748,JapicCTI-184195