Trial Outcomes & Findings for S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma (NCT NCT00124579)
NCT ID: NCT00124579
Last Updated: 2018-08-09
Results Overview
Responses are defined as follows: Complete Remission: Absence of bone marrow or blood findings of multiple myeloma. This includes disappearance of all evidence of serum and urine M-proteins on immunofixation electrophoresis studies. Normalization of serum concentrations of normal immunoglobulins is not required for CR. There must also be no evidence of increasing anemia. Bone marrow cellularity must be ≥ 20% with plasma cells ≤ 5%. Remission: A ≥ 75% reduction in the serum M-protein, and if a urine M-protein (Bence-Jones protein) is present, either a ≥ 90% reduction in this protein, or a urine M-protein \< 0.2gm/day. Bone marrow plasma cells must be ≤ 5%. Partial Remission: A ≥ 50% reduction in the serum M-protein, and if present, a ≥ 50% reduction in the urine M-protein (Bence-Jones protein). Bone marrow plasma cells must not be increased from baseline level.
TERMINATED
PHASE2
7 participants
1 year
2018-08-09
Participant Flow
Participant milestones
| Measure |
Bortezomib With Thalidomide and Dexamethasone Induction
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
Induction
STARTED
|
7
|
|
Induction
COMPLETED
|
2
|
|
Induction
NOT COMPLETED
|
5
|
|
Maintenance
STARTED
|
2
|
|
Maintenance
COMPLETED
|
0
|
|
Maintenance
NOT COMPLETED
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
S0417 Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Bortezomib With Thalidomide and Dexamethasone
n=7 Participants
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
Age, Continuous
|
63.7 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: Ninety patients is sufficient to distinguish between the null hypothesis that the response rate is 45% versus the alternative of a response rate of 60% with 89% power, using a one-sided test based on the binomial distribution with a significance level of 5%.
Responses are defined as follows: Complete Remission: Absence of bone marrow or blood findings of multiple myeloma. This includes disappearance of all evidence of serum and urine M-proteins on immunofixation electrophoresis studies. Normalization of serum concentrations of normal immunoglobulins is not required for CR. There must also be no evidence of increasing anemia. Bone marrow cellularity must be ≥ 20% with plasma cells ≤ 5%. Remission: A ≥ 75% reduction in the serum M-protein, and if a urine M-protein (Bence-Jones protein) is present, either a ≥ 90% reduction in this protein, or a urine M-protein \< 0.2gm/day. Bone marrow plasma cells must be ≤ 5%. Partial Remission: A ≥ 50% reduction in the serum M-protein, and if present, a ≥ 50% reduction in the urine M-protein (Bence-Jones protein). Bone marrow plasma cells must not be increased from baseline level.
Outcome measures
| Measure |
Bortezomib + Thal/Dex
n=7 Participants
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
Overall Response Rate Complete Remission (CR), Remission (R), and Partial Remission (PR).
|
14 percentage of participants
|
SECONDARY outcome
Timeframe: From date of protocol therapy start to date of protocol therapy end, i.e., up to about 3.5 yearsPopulation: All participants receiving at least one dose of induction therapy
To evaluate the qualitative and quantitative toxicities associated with this regimen.
Outcome measures
| Measure |
Bortezomib + Thal/Dex
n=7 Participants
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
Toxicity Evaluation
Muscle weakness, not d/t neuropathy - Extrem-lower
|
1 Participants
|
|
Toxicity Evaluation
Muscle weakness, not d/t neuropathy - body/general
|
1 Participants
|
|
Toxicity Evaluation
Albumin, serum-low (hypoalbuminemia)
|
1 Participants
|
|
Toxicity Evaluation
Allergy/Immunology-Other
|
1 Participants
|
|
Toxicity Evaluation
Bilirubin (hyperbilirubinemia)
|
1 Participants
|
|
Toxicity Evaluation
Edema: limb
|
1 Participants
|
|
Toxicity Evaluation
Extremity-lower (gait/walking)
|
1 Participants
|
|
Toxicity Evaluation
Fatigue (asthenia, lethargy, malaise)
|
1 Participants
|
|
Toxicity Evaluation
Hemoglobin
|
1 Participants
|
|
Toxicity Evaluation
Inf (clin/microbio) w/Gr 3-4 neuts - Lung
|
1 Participants
|
|
Toxicity Evaluation
Leukocytes (total WBC)
|
1 Participants
|
|
Toxicity Evaluation
Lymphopenia
|
1 Participants
|
|
Toxicity Evaluation
Neuropathy: motor
|
1 Participants
|
|
Toxicity Evaluation
Neuropathy: sensory
|
1 Participants
|
|
Toxicity Evaluation
Neutrophils/granulocytes (ANC/AGC)
|
2 Participants
|
|
Toxicity Evaluation
Platelets
|
1 Participants
|
SECONDARY outcome
Timeframe: about 12-18 monthsPopulation: With ninety patients, we will have 82% power to rule out a null hypothesis of a 12-month median survival versus an alternative hypothesis of an 18-month median survival at a significance level of 5%.
From date of initial registration to date of progression/relapse of disease (\> 25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc.) or death from any cause, whichever came first, up to 5 years
Outcome measures
| Measure |
Bortezomib + Thal/Dex
n=7 Participants
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
Progression-Free Survival
|
8 Months
Interval 4.0 to 12.0
|
Adverse Events
Bortezomib + Thal/Dex
Serious adverse events
| Measure |
Bortezomib + Thal/Dex
n=7 participants at risk
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
General disorders
Edema: limb
|
14.3%
1/7
|
|
Investigations
Bilirubin (hyperbilirubinemia)
|
14.3%
1/7
|
|
Investigations
Platelets
|
14.3%
1/7
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
14.3%
1/7
|
Other adverse events
| Measure |
Bortezomib + Thal/Dex
n=7 participants at risk
Induction (per 21-day cycle): Bortezomib - 1.0 mg/m2 (Days 1, 4, 8, and 11). Dexamethasone - 20 mg/d PO (Days 1, 2, 4, 5, 8, 9, 11, and 12). Thalidomide 100 mg (Days 1-21).
Maintenance (per 28-day cycle): thalidomide 100mg (Days 1-28). Dexamethasone 40 mg Days 1-4.
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin
|
85.7%
6/7
|
|
Cardiac disorders
SVT and nodal arrhythmia - Atrial fibrillation
|
14.3%
1/7
|
|
Cardiac disorders
SVT and nodal arrhythmia - Sinus bradycardia
|
14.3%
1/7
|
|
Endocrine disorders
Cushingoid appearance
|
14.3%
1/7
|
|
Eye disorders
Night blindness (nyctalopia)
|
14.3%
1/7
|
|
Eye disorders
Vision-blurred vision
|
14.3%
1/7
|
|
Eye disorders
Watery eye (epiphora, tearing)
|
14.3%
1/7
|
|
Gastrointestinal disorders
Constipation
|
100.0%
7/7
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
1/7
|
|
Gastrointestinal disorders
Distention/bloating, abdominal
|
14.3%
1/7
|
|
Gastrointestinal disorders
Flatulence
|
14.3%
1/7
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
14.3%
1/7
|
|
Gastrointestinal disorders
Nausea
|
42.9%
3/7
|
|
Gastrointestinal disorders
Pain - Abdomen NOS
|
28.6%
2/7
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
2/7
|
|
General disorders
Edema: head and neck
|
14.3%
1/7
|
|
General disorders
Edema: limb
|
42.9%
3/7
|
|
General disorders
Extremity-lower (gait/walking)
|
28.6%
2/7
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
100.0%
7/7
|
|
General disorders
Fever in absence of neutropenia, ANC lt1.0x10e9/L
|
28.6%
2/7
|
|
General disorders
Pain-Other
|
28.6%
2/7
|
|
General disorders
Rigors/chills
|
14.3%
1/7
|
|
Immune system disorders
Allergy/Immunology-Other
|
14.3%
1/7
|
|
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Bladder
|
14.3%
1/7
|
|
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Lung
|
14.3%
1/7
|
|
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Skin
|
14.3%
1/7
|
|
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Soft tiss
|
14.3%
1/7
|
|
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway
|
14.3%
1/7
|
|
Infections and infestations
Infection with unknown ANC - Upper airway NOS
|
14.3%
1/7
|
|
Infections and infestations
Infection-Other
|
14.3%
1/7
|
|
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)
|
28.6%
2/7
|
|
Investigations
AST, SGOT
|
14.3%
1/7
|
|
Investigations
Alkaline phosphatase
|
28.6%
2/7
|
|
Investigations
Bilirubin (hyperbilirubinemia)
|
28.6%
2/7
|
|
Investigations
Creatinine
|
28.6%
2/7
|
|
Investigations
Leukocytes (total WBC)
|
57.1%
4/7
|
|
Investigations
Lymphopenia
|
14.3%
1/7
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
42.9%
3/7
|
|
Investigations
Platelets
|
57.1%
4/7
|
|
Investigations
Weight gain
|
14.3%
1/7
|
|
Investigations
Weight loss
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
57.1%
4/7
|
|
Metabolism and nutrition disorders
Anorexia
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
57.1%
4/7
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
71.4%
5/7
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
14.3%
1/7
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
28.6%
2/7
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - Extrem-lower
|
28.6%
2/7
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
Pain - Back
|
28.6%
2/7
|
|
Musculoskeletal and connective tissue disorders
Pain - Bone
|
14.3%
1/7
|
|
Musculoskeletal and connective tissue disorders
Pain - Extremity-limb
|
28.6%
2/7
|
|
Musculoskeletal and connective tissue disorders
Pain - Joint
|
28.6%
2/7
|
|
Musculoskeletal and connective tissue disorders
Pain - Neck
|
14.3%
1/7
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain
|
14.3%
1/7
|
|
Nervous system disorders
Dizziness
|
14.3%
1/7
|
|
Nervous system disorders
Neurology-Other
|
14.3%
1/7
|
|
Nervous system disorders
Neuropathy: motor
|
14.3%
1/7
|
|
Nervous system disorders
Neuropathy: sensory
|
85.7%
6/7
|
|
Nervous system disorders
Pain - Head/headache
|
14.3%
1/7
|
|
Nervous system disorders
Tremor
|
28.6%
2/7
|
|
Psychiatric disorders
Confusion
|
14.3%
1/7
|
|
Psychiatric disorders
Insomnia
|
14.3%
1/7
|
|
Psychiatric disorders
Mood alteration - depression
|
14.3%
1/7
|
|
Renal and urinary disorders
Glomerular filtration rate
|
14.3%
1/7
|
|
Renal and urinary disorders
Proteinuria
|
28.6%
2/7
|
|
Reproductive system and breast disorders
Sexual/Reproductive Function-Other (Specify)
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
42.9%
3/7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
57.1%
4/7
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, Respiratory tract NOS
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Nose
|
14.3%
1/7
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory-Other
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
28.6%
2/7
|
|
Skin and subcutaneous tissue disorders
Rash: erythema multiforme
|
14.3%
1/7
|
|
Skin and subcutaneous tissue disorders
Skin breakdown/decubitus ulcer
|
14.3%
1/7
|
|
Vascular disorders
Hypotension
|
14.3%
1/7
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place