Trial Outcomes & Findings for Combination Bisphosphonate and Anti-Angiogenesis Therapy With Pamidronate and Thalidomide (NCT NCT00083382)
NCT ID: NCT00083382
Last Updated: 2015-06-24
Results Overview
Best response to study treatment as defined by protocol-specific response criteria: Complete Response (CR) = absence of urine and serum M-components by immunofixation; bone marrow should be adequately cellular (\>20%) with \<1% monoclonal plasma cells by DNA-clg flow cytometry; serum calcium level must be normal; no new bone lesions nor enlargement of existing lesions; Normalization of serum concentrations of normal immunoglobulins is not required for CR. Partial Response (PR) = Reduction by \> 75% in serum myeloma protein production; Decrease in monoclonal marrow plasmacytosis to \<5%; Decrease in Bence-Jones proteinuria by \>90%; No new lytic bone lesions or soft tissue plasmacytoma. Treatment Failures/Progressive Disease (PD) = Such patients do not fulfill the above criteria and/or have new lytic lesions (but not compression fractures), hypercalcemia, or other new manifestations of disease.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
83 participants
Primary outcome timeframe
2 years
Results posted on
2015-06-24
Participant Flow
Participant milestones
| Measure |
Thalidomide + Bisphosphonate
200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
Thalidomide: All Patients will receive thalidomide 200 mg as an oral once daily dose. Dose may be reduced to as low as 50 mg qod in the event of severe toxicity. Thalidomide will continue daily as tolerated until criteria to remove from study are met. Patients will receive appropriate regimen to prevent constipation (i.e., colace, dulcolax, milk of magnesia, or lactulose)
Pamidronate: Patients will receive either pamidronate or zometa. Pamidronate is administered at a dose of 90 mg by continuous infusion over 90 minutes, every two weeks for 2 months. Disease will be reassessed after two cycles. Those with stable disease or better will receive 90 mg every 4 weeks as maintenance therapy.
Zometa: Patients will receive either pamidronate or zometa. Zometa is administered at a dose of 4 mg by continuous infusion every two weeks for 2 months. Dise
|
|---|---|
|
Overall Study
STARTED
|
83
|
|
Overall Study
COMPLETED
|
83
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combination Bisphosphonate and Anti-Angiogenesis Therapy With Pamidronate and Thalidomide
Baseline characteristics by cohort
| Measure |
Thalidomide + Bisphosphonate
n=83 Participants
200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
|
|---|---|
|
Age, Continuous
|
60.0 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsBest response to study treatment as defined by protocol-specific response criteria: Complete Response (CR) = absence of urine and serum M-components by immunofixation; bone marrow should be adequately cellular (\>20%) with \<1% monoclonal plasma cells by DNA-clg flow cytometry; serum calcium level must be normal; no new bone lesions nor enlargement of existing lesions; Normalization of serum concentrations of normal immunoglobulins is not required for CR. Partial Response (PR) = Reduction by \> 75% in serum myeloma protein production; Decrease in monoclonal marrow plasmacytosis to \<5%; Decrease in Bence-Jones proteinuria by \>90%; No new lytic bone lesions or soft tissue plasmacytoma. Treatment Failures/Progressive Disease (PD) = Such patients do not fulfill the above criteria and/or have new lytic lesions (but not compression fractures), hypercalcemia, or other new manifestations of disease.
Outcome measures
| Measure |
Thalidomide + Bisphosphonate
n=83 Participants
200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
|
|---|---|
|
Best Response
Treatment Failure/Progressive Disease
|
56 participants
|
|
Best Response
Partial Response
|
17 participants
|
|
Best Response
Complete Response
|
10 participants
|
Adverse Events
Thalidomide + Bisphosphonate
Serious events: 16 serious events
Other events: 83 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Thalidomide + Bisphosphonate
n=83 participants at risk
200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/infiltrates
|
2.4%
2/83
|
|
Cardiac disorders
Cardiovascular-other
|
3.6%
3/83
|
|
Musculoskeletal and connective tissue disorders
Joint, muscle, bone-other
|
1.2%
1/83
|
|
Respiratory, thoracic and mediastinal disorders
Lung-other
|
1.2%
1/83
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory infect w/o neutrop
|
2.4%
2/83
|
|
Gastrointestinal disorders
Diarrhea without colostomy
|
1.2%
1/83
|
|
General disorders
Fatigue/malaise/lethargy
|
1.2%
1/83
|
|
Cardiac disorders
Syncope
|
1.2%
1/83
|
|
Psychiatric disorders
Confusion
|
1.2%
1/83
|
|
General disorders
Speech impairment
|
1.2%
1/83
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
1.2%
1/83
|
|
Gastrointestinal disorders
GI-other
|
1.2%
1/83
|
Other adverse events
| Measure |
Thalidomide + Bisphosphonate
n=83 participants at risk
200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
|
|---|---|
|
Immune system disorders
Grade 1 Allergic rhinitis
|
8.4%
7/83
|
|
Blood and lymphatic system disorders
Grade 1 Anemia
|
30.1%
25/83
|
|
Blood and lymphatic system disorders
Grade 2 Anemia
|
9.6%
8/83
|
|
Blood and lymphatic system disorders
Grade 1 Neutropenia/granulocytopenia
|
12.0%
10/83
|
|
Blood and lymphatic system disorders
Grade 2 Neutropenia/granulocytopenia
|
20.5%
17/83
|
|
Blood and lymphatic system disorders
Grade 1 Thrombocytopenia
|
20.5%
17/83
|
|
Blood and lymphatic system disorders
Grade 2 Thrombocytopenia
|
6.0%
5/83
|
|
Blood and lymphatic system disorders
Grade 3 Thrombocytopenia
|
6.0%
5/83
|
|
Blood and lymphatic system disorders
Grade 2 Leukopenia
|
24.1%
20/83
|
|
Cardiac disorders
Grade 1 Arrhythmia, NOS
|
10.8%
9/83
|
|
Cardiac disorders
Grade 4 Cardiovascular - other
|
4.8%
4/83
|
|
Cardiac disorders
Grade 1 Edema
|
32.5%
27/83
|
|
Cardiac disorders
Grade 2 Edema
|
9.6%
8/83
|
|
Cardiac disorders
Grade 1 Hypertension
|
4.8%
4/83
|
|
Cardiac disorders
Grade 2 Hypertension
|
4.8%
4/83
|
|
Cardiac disorders
Grade 1 Sinus bradycardia
|
8.4%
7/83
|
|
Cardiac disorders
Grade 2 Sinus bradycardia
|
6.0%
5/83
|
|
General disorders
Grade 1 Fatigue
|
27.7%
23/83
|
|
General disorders
Grade 2 Fatigue
|
50.6%
42/83
|
|
General disorders
Grade 3 Fatigue
|
10.8%
9/83
|
|
General disorders
Grade 1 Fever without neutropenia
|
4.8%
4/83
|
|
General disorders
Grade 2 Fever without neutropenia
|
9.6%
8/83
|
|
General disorders
Grade 1 Fever, NOS
|
25.3%
21/83
|
|
General disorders
Grade 2 Fever, NOS
|
14.5%
12/83
|
|
General disorders
Grade 2 Sweating
|
4.8%
4/83
|
|
General disorders
Grade 1 weight gain
|
7.2%
6/83
|
|
General disorders
Grade 2 weight gain
|
6.0%
5/83
|
|
General disorders
Grade 1 weight loss
|
8.4%
7/83
|
|
Skin and subcutaneous tissue disorders
Grade 1 Dry skin
|
12.0%
10/83
|
|
Skin and subcutaneous tissue disorders
Grade 1 Erythema/rash/eruption/desquamation
|
6.0%
5/83
|
|
Skin and subcutaneous tissue disorders
Grade 2 Erythema/rash/eruption/desquamation
|
10.8%
9/83
|
|
Skin and subcutaneous tissue disorders
Grade 1 Rash/desquamation
|
12.0%
10/83
|
|
Skin and subcutaneous tissue disorders
Grade 2 Rash/desquamation
|
8.4%
7/83
|
|
Skin and subcutaneous tissue disorders
Grade 1 Skin - other
|
7.2%
6/83
|
|
Skin and subcutaneous tissue disorders
Grade 2 Skin - other
|
4.8%
4/83
|
|
Gastrointestinal disorders
Grade 1 Anorexia
|
10.8%
9/83
|
|
Gastrointestinal disorders
Grade 2 Anorexia
|
6.0%
5/83
|
|
Gastrointestinal disorders
Grade 2 Constipation
|
6.0%
5/83
|
|
Gastrointestinal disorders
Grade 1 Constipation/bowel obstruction
|
28.9%
24/83
|
|
Gastrointestinal disorders
Grade 2 Constipation/bowel obstruction
|
38.6%
32/83
|
|
Gastrointestinal disorders
Grade 3 Constipation/bowel obstruction
|
4.8%
4/83
|
|
Gastrointestinal disorders
Grade 1 Diarrhea without colostomy
|
8.4%
7/83
|
|
Gastrointestinal disorders
Grade 2 Diarrhea without colostomy
|
10.8%
9/83
|
|
Gastrointestinal disorders
Grade 1 GI - other
|
8.4%
7/83
|
|
Gastrointestinal disorders
Grade 1 Mouth dryness
|
14.5%
12/83
|
|
Gastrointestinal disorders
Grade 2 Mouth dryness
|
10.8%
9/83
|
|
Gastrointestinal disorders
Grade 1 Nausea
|
13.3%
11/83
|
|
Gastrointestinal disorders
Grade 2 Nausea
|
9.6%
8/83
|
|
Gastrointestinal disorders
Grade 1 Vomiting
|
10.8%
9/83
|
|
Hepatobiliary disorders
Grade 1 Alkaline phosphatase increase
|
4.8%
4/83
|
|
Hepatobiliary disorders
Grade 1 Hypoalbuminemia
|
43.4%
36/83
|
|
Hepatobiliary disorders
Grade 2 Hypoalbuminemia
|
8.4%
7/83
|
|
Hepatobiliary disorders
Grade 1 SGOT (AST) increase
|
14.5%
12/83
|
|
Hepatobiliary disorders
Grade 1 SGPT (ALT) increase
|
22.9%
19/83
|
|
Infections and infestations
Grade 1 Infection w/o 3-4 neutropenia
|
7.2%
6/83
|
|
Infections and infestations
Grade 2 Infection w/o 3-4 neutropenia
|
10.8%
9/83
|
|
Infections and infestations
Grade 2 Respiratory infect w/o neutrop
|
6.0%
5/83
|
|
Metabolism and nutrition disorders
Grade 1 Bicarbonate decrease
|
22.9%
19/83
|
|
Metabolism and nutrition disorders
Grade 1 Hypercalcemia
|
4.8%
4/83
|
|
Metabolism and nutrition disorders
Grade 1 Hyperglycemia
|
38.6%
32/83
|
|
Metabolism and nutrition disorders
Grade 2 Hyperglycemia
|
13.3%
11/83
|
|
Metabolism and nutrition disorders
Grade 3 Hyperglycemia
|
7.2%
6/83
|
|
Metabolism and nutrition disorders
Grade 1 Hypocalcemia
|
47.0%
39/83
|
|
Metabolism and nutrition disorders
Grade 2 Hypocalcemia
|
10.8%
9/83
|
|
Metabolism and nutrition disorders
Grade 1 Hypokalemia
|
18.1%
15/83
|
|
Metabolism and nutrition disorders
Grade 1 Hypomagnesemia
|
56.6%
47/83
|
|
Metabolism and nutrition disorders
Grade 1 Hyponatremia
|
28.9%
24/83
|
|
Metabolism and nutrition disorders
Grade 3 Hyponatremia
|
4.8%
4/83
|
|
Metabolism and nutrition disorders
Grade 2 Hypophosphatemia
|
26.5%
22/83
|
|
Metabolism and nutrition disorders
Grade 3 Hypophosphatemia
|
10.8%
9/83
|
|
Musculoskeletal and connective tissue disorders
Grade 2 Arthritis
|
7.2%
6/83
|
|
Musculoskeletal and connective tissue disorders
Grade 1 Joint, muscle, bone - other
|
25.3%
21/83
|
|
Musculoskeletal and connective tissue disorders
Grade 2 Joint, muscle, bone - other
|
19.3%
16/83
|
|
Musculoskeletal and connective tissue disorders
Grade 3 Joint, muscle, bone - other
|
4.8%
4/83
|
|
Musculoskeletal and connective tissue disorders
Grade 1 Muscle Weakness (not neuro)
|
13.3%
11/83
|
|
Musculoskeletal and connective tissue disorders
Grade 2 Muscle Weakness (not neuro)
|
8.4%
7/83
|
|
Psychiatric disorders
Grade 1 Anxiety/agitation
|
12.0%
10/83
|
|
Psychiatric disorders
Grade 2 Anxiety/agitation
|
4.8%
4/83
|
|
Nervous system disorders
Grade 1 Ataxia
|
4.8%
4/83
|
|
Psychiatric disorders
Grade 1 Confusion
|
15.7%
13/83
|
|
Psychiatric disorders
Grade 2 Confusion
|
6.0%
5/83
|
|
Nervous system disorders
Grade 1 Cranial neuropathy
|
7.2%
6/83
|
|
Psychiatric disorders
Grade 1 Depression
|
22.9%
19/83
|
|
Psychiatric disorders
Grade 2 Depression
|
13.3%
11/83
|
|
Nervous system disorders
Grade 1 Dizziness/light headedness
|
16.9%
14/83
|
|
Nervous system disorders
Grade 2 Dizziness/light headedness
|
6.0%
5/83
|
|
Nervous system disorders
Grade 3 Dizziness/light headedness
|
8.4%
7/83
|
|
General disorders
Grade 1 Headache
|
12.0%
10/83
|
|
General disorders
Grade 2 Headache
|
8.4%
7/83
|
|
Psychiatric disorders
Grade 1 Insomnia
|
6.0%
5/83
|
|
Psychiatric disorders
Grade 2 Insomnia
|
6.0%
5/83
|
|
Psychiatric disorders
Grade 1 Memory loss
|
7.2%
6/83
|
|
Psychiatric disorders
Grade 1 Mood/consciousness change, NOS
|
10.8%
9/83
|
|
Nervous system disorders
Grade 1 Neuro - other
|
15.7%
13/83
|
|
Nervous system disorders
Grade 2 Neuro - other
|
4.8%
4/83
|
|
Nervous system disorders
Grade 1 Sensory neuropathy
|
47.0%
39/83
|
|
Nervous system disorders
Grade 2 Sensory neuropathy
|
38.6%
32/83
|
|
Nervous system disorders
Grade 3 Sensory neuropathy
|
10.8%
9/83
|
|
General disorders
Grade 1 Somnolence/consciousness loss
|
10.8%
9/83
|
|
General disorders
Grade 2 Somnolence/consciousness loss
|
6.0%
5/83
|
|
General disorders
Grade 3 Somnolence/consciousness loss
|
4.8%
4/83
|
|
Nervous system disorders
Grade 1 Tremor
|
14.5%
12/83
|
|
Nervous system disorders
Grade 2 Tremor
|
6.0%
5/83
|
|
Nervous system disorders
Grade 1 Weakness (motor neuropathy)
|
18.1%
15/83
|
|
Nervous system disorders
Grade 2 Weakness (motor neuropathy)
|
13.3%
11/83
|
|
Nervous system disorders
Grade 3 Weakness (motor neuropathy)
|
7.2%
6/83
|
|
Eye disorders
Grade 2 Blurred vision
|
14.5%
12/83
|
|
Eye disorders
Grade 1 Eye - other
|
9.6%
8/83
|
|
General disorders
Grade 1 Bone Pain
|
16.9%
14/83
|
|
General disorders
Grade 2 Bone Pain
|
15.7%
13/83
|
|
General disorders
Grade 3 Bone Pain
|
7.2%
6/83
|
|
General disorders
Grade 1 Chest pain, not cardio or pleural
|
4.8%
4/83
|
|
General disorders
Grade 2 Lower Back
|
4.8%
4/83
|
|
General disorders
Grade 1 Pain - other
|
12.0%
10/83
|
|
General disorders
Grade 2 Pain - other
|
12.0%
10/83
|
|
General disorders
Grade 3 Pain - other
|
6.0%
5/83
|
|
General disorders
Grade 1 Upper Back
|
7.2%
6/83
|
|
Respiratory, thoracic and mediastinal disorders
Grade 1 Cough
|
8.4%
7/83
|
|
Respiratory, thoracic and mediastinal disorders
Grade 2 Cough
|
7.2%
6/83
|
|
Respiratory, thoracic and mediastinal disorders
Grade 2 Dyspnea
|
22.9%
19/83
|
|
Respiratory, thoracic and mediastinal disorders
Grade 3 Dyspnea
|
6.0%
5/83
|
|
Respiratory, thoracic and mediastinal disorders
Grade 3 Pneumonitis/infiltrates
|
4.8%
4/83
|
|
Renal and urinary disorders
Grade 1 Creatinine increase
|
16.9%
14/83
|
|
Renal and urinary disorders
Grade 2 Creatinine increase
|
6.0%
5/83
|
|
Renal and urinary disorders
Grade 1 GU - other
|
4.8%
4/83
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place