Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Venetoclax
Product Code: ABT-199 (GDC-0199)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Venetoclax
CAS Nu
Sponsors
AbbVie Deutschland GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject must have documented, confirmed active MM with = 10% clonal bone marrow plasma cells or biopsy-proven bone or extramedullary plasmacytoma and any one or more of the following myeloma-defining events: • Evidence of end organ damage attributed to the underlying plasma cell proliferative disorder and satisfying at least one of the CRAB criteria: 1. Hypercalcemia (serum calcium > 0.25 mmol/L [> 1 mg/dL] higher than the upper limit of normal (ULN) or > 2.75 mmol/L [> 11 mg/dL]); 2. Renal insufficiency (creatinine clearance [CrCL] 177 µmol/L [> 2 mg/dL]); 3. Anemia (hemoglobin > 20 g/L below the lower limit of normal or hemoglobin 1 focal lesions on magnetic resonance imaging (MRI; each focal lesion must be 5 mm or more in size). - Subject must have measurable disease defined by at least one of the following criteria: • Serum M-protein = 1.0 g/dL (immunoglobulin [Ig]G myeloma) or = 0.5 g/dL (IgA, IgM, IgD, or IgE myeloma); • Urine M-protein = 200 mg/24 hours; • Serum free light chain (FLC) = 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal. - Subject is newly diagnosed and not considered a candidate for high-dose therapy and hematopoietic stem cell transplantation (HSCT) due to: • Age = 65 years; • Or age less than ( 50% myeloma involvement in the marrow, a platelet count of = 50,000 mm3 is allowed. Subjects may not have received a platelet transfusion within 72 hours prior to the platelet count used for eligibility; • Hemoglobin = 8.0 g/dL; subject may receive red blood cell transfusions in accordance with institutional guidelines to meet this criteria; • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × upper limit of normal (ULN); • Total bilirubin = 1
Exclusion criteria
Exclusion criteria: • The subject is not naïve to treatment with venetoclax or another BCL-2 inhibitor • The subject has been treated or received any of the following: o Prior or current systemic therapy or HSCT for MM o Radiation therapy within 2 weeks of dosing o Plasmapheresis within 4 weeks of dosing o Immunization with live vaccine within 8 weeks of dosing • The subject has a history of other active malignancies, including myelodysplastic syndromes (MDS) within the past three years except adequately treated in situ carcinoma of the cervix, uteri or the breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen levels off treatment; previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study. • The subject has known allergies, hypersensitivities, or intolerance to any of the study drug or excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and preliminary efficacy of venetoclax plus lenalidomide and dexamethasone in subjects with newly diagnosed t(11;14)-positive MM who are ineligible for high-dose therapy.; Secondary Objective: - To characterize the plasma pharmacokinetics (PK) of venetoclax and lenalidomide when co-administered in subjects with newly diagnosed t(11;14)-positive MM who are ineligible for high-dose therapy and who are also receiving dexamethasone as part of the treatment regimen. - The exploratory objective of this study is to evaluate correlative biomarkers of venetoclax plus lenalidomide and dexamethasone including, but not limited to, BCL-2 family member expression and chromosomal abnormalities. ;Primary end point(s): - Percent of subjects who achieve a complete response (CR) or better by International Myeloma Working Group (IMWG) criteria.;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Very good partial response (VGPR) or better • Overall response rate (ORR) – includes partial response (PR) or better • Time to response (TTR) • Duration of response (DOR) • Progression-free survival (PFS) • MRD negativity rate at 12 months • Time to disease progression (TTP) • Time to next treatment (TTNT) • Overall survival (OS) • Percent of subjects who achieve minimal residual disease negativity. ;Timepoint(s) of evaluation of this end point: 7 years | — |
Countries
Australia, Canada, European Union, Spain, United States
Contacts
Public ContactEU Clinical Trials Helpdesk
AbbVie Ltd.
Outcome results
None listed