Trial Outcomes & Findings for Vorinostat,Lenalinomide and Dexamethasone in Multiple Myeloma Refractory to Previous Lenalinomide Containing Regimens (NCT NCT01502085)
NCT ID: NCT01502085
Last Updated: 2022-01-21
Results Overview
Defined as: 1. Progression on therapy OR within 60 days after the last dose of a lenalidomide containing regimen OR 2. No clinical response (\<MR) on a lenalidomide containing regimen An overall response rate of 25% or more will be acceptable, while an overall response of less than or equal to 16% will be considered unacceptable. Response will be assessed according to a modified International Working Group Uniform Response Criteria (Durie et al., 2006) * Complete Response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and ⩽5% plasma cells in bone marrow * Very Good Partial Response- Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component \<100 mg per 24 h * Partial Response- ⩾50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ⩾90% or to \<200 mg per 24 h.
COMPLETED
PHASE1/PHASE2
25 participants
On treatment portion of study is completed after 12 cycles (each cycle is 28 days in duration) and one month of follow up. Patients may be followed for up to two years after last dose of lenalidomide and vorinostat for disease status and survival.
2022-01-21
Participant Flow
Participant milestones
| Measure |
Vorinostat, Lenalinomide, Dexamethasone
Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
Vorinostat, Lenalinomide and Dexamethasone: Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21
\* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert
Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Vorinostat,Lenalinomide and Dexamethasone in Multiple Myeloma Refractory to Previous Lenalinomide Containing Regimens
Baseline characteristics by cohort
| Measure |
Vorinostat, Lenalinomide, Dexamethasone
n=25 Participants
Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
Vorinostat, Lenalinomide and Dexamethasone: Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21
\* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert
Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
|
|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: On treatment portion of study is completed after 12 cycles (each cycle is 28 days in duration) and one month of follow up. Patients may be followed for up to two years after last dose of lenalidomide and vorinostat for disease status and survival.Defined as: 1. Progression on therapy OR within 60 days after the last dose of a lenalidomide containing regimen OR 2. No clinical response (\<MR) on a lenalidomide containing regimen An overall response rate of 25% or more will be acceptable, while an overall response of less than or equal to 16% will be considered unacceptable. Response will be assessed according to a modified International Working Group Uniform Response Criteria (Durie et al., 2006) * Complete Response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and ⩽5% plasma cells in bone marrow * Very Good Partial Response- Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component \<100 mg per 24 h * Partial Response- ⩾50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ⩾90% or to \<200 mg per 24 h.
Outcome measures
| Measure |
Vorinostat, Lenalinomide, Dexamethasone
n=25 Participants
Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
Vorinostat, Lenalinomide and Dexamethasone: Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21
\* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert
Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
|
|---|---|
|
Overall Response Rate (PR or Better) of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed/Refractory MM Refractory to a Previous Lenalidomide Containing Regimen
|
6 Participants
|
Adverse Events
Vorinostat, Lenalinomide, Dexamethasone
Serious adverse events
| Measure |
Vorinostat, Lenalinomide, Dexamethasone
n=25 participants at risk
Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
Vorinostat, Lenalinomide and Dexamethasone: Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21
\* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert
Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
|
|---|---|
|
Nervous system disorders
Syncopal Episode
|
8.0%
2/25 • Number of events 2
|
|
Nervous system disorders
Dizziness
|
4.0%
1/25 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
4.0%
1/25 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Left Groin Pain
|
4.0%
1/25 • Number of events 1
|
|
Renal and urinary disorders
Acute Renal Failure
|
4.0%
1/25 • Number of events 1
|
|
Infections and infestations
Viral Syndrome/Neutropenia
|
4.0%
1/25 • Number of events 1
|
Other adverse events
| Measure |
Vorinostat, Lenalinomide, Dexamethasone
n=25 participants at risk
Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21 \* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
Vorinostat, Lenalinomide and Dexamethasone: Vorinostat: 400 mg po days 1-7 and 15-21 Lenalidomide: 25 mg po days 1-21
\* Lenalidomide dose for patients with renal impairment (CrCL\<50ml/min) has be dose adjusted according to package insert
Dexamethasone: 40mg po days 1, 8, 15 and 22 for patients aged less than 75 years, 20mg for those aged 75 years and above
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
68.0%
17/25
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
56.0%
14/25
|
|
Blood and lymphatic system disorders
Anemia
|
52.0%
13/25
|
|
General disorders
Fatigue
|
72.0%
18/25
|
|
Gastrointestinal disorders
Diarrhea
|
72.0%
18/25
|
|
Nervous system disorders
Dysgeusia
|
28.0%
7/25
|
|
Gastrointestinal disorders
Nausea
|
28.0%
7/25
|
|
Gastrointestinal disorders
Anorexia
|
28.0%
7/25
|
|
Blood and lymphatic system disorders
Hyperglycemia
|
20.0%
5/25
|
|
Gastrointestinal disorders
Abdominal Bloating
|
16.0%
4/25
|
|
Hepatobiliary disorders
Elevated Liver Function Tests
|
16.0%
4/25
|
|
Skin and subcutaneous tissue disorders
Scalp Pruritus
|
16.0%
4/25
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.0%
4/25
|
|
Musculoskeletal and connective tissue disorders
Muscle Cramping
|
16.0%
4/25
|
|
Gastrointestinal disorders
Constipation
|
16.0%
4/25
|
|
General disorders
Weight Loss
|
16.0%
4/25
|
|
Nervous system disorders
Peripheral Neuropathy
|
16.0%
4/25
|
|
Gastrointestinal disorders
Vomiting
|
12.0%
3/25
|
|
General disorders
Abdominal Discomfort
|
12.0%
3/25
|
|
Psychiatric disorders
Mood Alteration
|
12.0%
3/25
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place