Clinical Trials List
Protocol NumberM14-031
NCT Number(ClinicalTrials.gov Identfier)NCT02755597
2016-12-01 - 2019-12-31
Phase III
Terminated5
ICD-10C90.00
Multiple myeloma not having achieved remission
A Phase 3, Multicenter, Randomized, Double Blind, Study of Bortezomib and Dexamethasone in Combination with Either Venetoclax or Placebo in Subjects with Relapsed or Refractory Multiple Myeloma Who are Sensitive or Naïve to Proteasome Inhibitors
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- Su-Peng Yeh Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Po-Shen Ko Division of Hematology & Oncology
- Jyh-Pyng Gau Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
5 Stop recruiting
Audit
None
Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- MING YAO Division of Hematology & Oncology
- Chien-Yuan Chen Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Sheng-chieh Chou Division of Hematology & Oncology
- Chien-Yuan Chen Division of Hematology & Oncology
- Shang-Yi Huang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Relapsed or Refractory Multiple Myeloma
Objectives
The primary objective of the study is to compare the progression-free survival (PFS) between treatment arms in subjects with relapsed or refractory multiple myeloma who are considered sensitive or naïve to proteasome inhibitors and received 1 to 3 prior lines of therapy for multiple myeloma.
The secondary objectives are to compare, between treatment arms, the following: Very Good Partial Response (VGPR) or better response rate; PFS in subjects with high BCL-2 expression; duration of response (DOR); Patient Reported Outcomes (PRO) including Worst Pain (Brief Pain Inventory – Short Form [BPI-SF]), Physical Functioning and Global Health Status/Quality of Life (GHS/QoL) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core [EORTC QLQ C30]), and Fatigue (Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF]); overall survival (OS); time to disease progression (TTP); objective response rate (ORR); minimal residual disease (MRD) status; and safety.
Test Drug
Venetoclax (ABT-199)
Active Ingredient
Venetoclax
Dosage Form
Tablet
Dosage
100
Endpoints
Efficacy:
IMWG assessments for clinical response and progressive disease will be done per IMWG criteria, and will be used to assess PFS, VGPR or better response rate, DOR, TTP, and ORR.
OS will be evaluated according to survival information (i.e., alive or deceased, and if deceased, date and cause of death) and post treatment information (including therapy, dates of therapy and response).
PROs will be evaluated using BPI-SF, EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20), PROMIS Cancer Fatigue SF, and EuroQoL EQ-5D-5L (EQ-5D-5L).
IMWG assessments for clinical response and progressive disease will be done per IMWG criteria, and will be used to assess PFS, VGPR or better response rate, DOR, TTP, and ORR.
OS will be evaluated according to survival information (i.e., alive or deceased, and if deceased, date and cause of death) and post treatment information (including therapy, dates of therapy and response).
PROs will be evaluated using BPI-SF, EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20), PROMIS Cancer Fatigue SF, and EuroQoL EQ-5D-5L (EQ-5D-5L).
Inclution Criteria
Main Inclusion:
1. Eastern Collaborative Oncology Group (ECOG) performance score of ≤ 2.
2. Subjects has documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy.
• Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet criteria for refractory myeloma.
• Refractory myeloma is defined as disease that is nonresponsive (failure to achieve minimal response or development of PD) while on primary or salvage therapy, or progresses within 60 days of last therapy.
3. Subject must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma.
• A line of therapy consists of ≥ 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.
4. Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided: ALL of the following criteria are met:
• Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per IMWG or European Society for Blood and Marrow Transplantation [EBMT] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND
• Best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a Partial Response (PR), AND
• Subject did not discontinue any proteasome inhibitor due to intolerance or ≥ Grade 3 related toxicity.
5. Subject has measurable disease at Screening, defined at least one of the following:
• Serum M-protein ≥ 0.5 gram (g)/deciliter (dL), OR
• Urine M-protein ≥ 200 mg in 24 hours, OR
• Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
6. Subjects must meet the following laboratory parameters, per laboratory reference range:
• Absolute neutrophil count (ANC) ≥ 1000/microliter (µL) within 2 weeks prior to randomization; subjects may use growth factor support to achieve ANC eligibility criteria.
• Platelet count ≥ 50,000 millimeter (mm)3, within 2 weeks prior to randomization. For subjects with > 50% myeloma involvement in the bone marrow, a platelet count of ≥ 30,000 mm3, within 2 weeks prior to randomization 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, within 2 weeks prior to randomization. Subjects may receive red blood cell (RBC) transfusions in accordance with institutional guidelines to meet this criteria.
• AST and ALT ≤ 3 × upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN with the approval of the Primary Therapeutic Area Medical Director (TA MD).
• Creatinine clearance (CrCl) ≥ 30 milliliter (mL)/minute (min) measured by 24-hour urine collection or calculated using the Cockcroft-Gault formula.
1. Eastern Collaborative Oncology Group (ECOG) performance score of ≤ 2.
2. Subjects has documented relapsed or progressive multiple myeloma on or after any regimen or is refractory to the most recent line of therapy.
• Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet criteria for refractory myeloma.
• Refractory myeloma is defined as disease that is nonresponsive (failure to achieve minimal response or development of PD) while on primary or salvage therapy, or progresses within 60 days of last therapy.
3. Subject must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma.
• A line of therapy consists of ≥ 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.
4. Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided: ALL of the following criteria are met:
• Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per IMWG or European Society for Blood and Marrow Transplantation [EBMT] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND
• Best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a Partial Response (PR), AND
• Subject did not discontinue any proteasome inhibitor due to intolerance or ≥ Grade 3 related toxicity.
5. Subject has measurable disease at Screening, defined at least one of the following:
• Serum M-protein ≥ 0.5 gram (g)/deciliter (dL), OR
• Urine M-protein ≥ 200 mg in 24 hours, OR
• Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
6. Subjects must meet the following laboratory parameters, per laboratory reference range:
• Absolute neutrophil count (ANC) ≥ 1000/microliter (µL) within 2 weeks prior to randomization; subjects may use growth factor support to achieve ANC eligibility criteria.
• Platelet count ≥ 50,000 millimeter (mm)3, within 2 weeks prior to randomization. For subjects with > 50% myeloma involvement in the bone marrow, a platelet count of ≥ 30,000 mm3, within 2 weeks prior to randomization 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, within 2 weeks prior to randomization. Subjects may receive red blood cell (RBC) transfusions in accordance with institutional guidelines to meet this criteria.
• AST and ALT ≤ 3 × upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN with the approval of the Primary Therapeutic Area Medical Director (TA MD).
• Creatinine clearance (CrCl) ≥ 30 milliliter (mL)/minute (min) measured by 24-hour urine collection or calculated using the Cockcroft-Gault formula.
Exclusion Criteria
Main Exclusion:
1. Subject is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.
2. Subject has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.
3. Subject has any of the following conditions:
• Non-secretory or oligo-secretory multiple myeloma
• Active plasma cell leukemia, i.e., either 20% of peripheral white blood cells or > 2.0 × 109/Liter (L) circulating plasma cells by standard differential
• Waldenström's macroglobulinemia
• Amyloidosis
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome)
• Known Human Immunodeficiency Viral (HIV) infection
• Active hepatitis B or C infection based on blood screen tests
• Significant cardiovascular disease, including uncontrolled angina, hypertension, arrhythmia, recent myocardial infarction within 6 months of randomization, congestive heart failure New York Heart Association (NYHA) Class ≥ 3
• Major surgery within 4 weeks prior to randomization
• Acute infections requiring parenteral therapy (antibiotic, antifungal or antiviral) within 14 days prior to randomization
• Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to randomization
• Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization
• Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study
4. Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions:
• 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 (PSA) 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.
5. If subject had prior stem cell transplant (SCT), subject has evidence of ongoing graft versus host disease (GvHD).
1. Subject is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.
2. Subject has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.
3. Subject has any of the following conditions:
• Non-secretory or oligo-secretory multiple myeloma
• Active plasma cell leukemia, i.e., either 20% of peripheral white blood cells or > 2.0 × 109/Liter (L) circulating plasma cells by standard differential
• Waldenström's macroglobulinemia
• Amyloidosis
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome)
• Known Human Immunodeficiency Viral (HIV) infection
• Active hepatitis B or C infection based on blood screen tests
• Significant cardiovascular disease, including uncontrolled angina, hypertension, arrhythmia, recent myocardial infarction within 6 months of randomization, congestive heart failure New York Heart Association (NYHA) Class ≥ 3
• Major surgery within 4 weeks prior to randomization
• Acute infections requiring parenteral therapy (antibiotic, antifungal or antiviral) within 14 days prior to randomization
• Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to randomization
• Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization
• Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study
4. Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions:
• 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 (PSA) 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.
5. If subject had prior stem cell transplant (SCT), subject has evidence of ongoing graft versus host disease (GvHD).
The Estimated Number of Participants
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Taiwan
15 participants
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Global
280 participants
