Trial Outcomes & Findings for Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone (NCT NCT00522392)

Last Updated: 2015-06-26

Results Overview

Progression-free survival was defined as the time from randomization to the earliest documentation of disease progression (PD) or death. If a patient died without evidence of PD, the patient was considered an event if death occurred within 3 months of the last disease assessment. Patients who died outside of the specified interval or patients who were alive without evidence of PD were censored at the date of last disease assessment. The PFS results are based on data as of August 2012, while overall survival (OS) was updated in April 2014. Given the early termination and limited sample size, data management efforts to update PFS were not pursued.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

48 participants

Primary outcome timeframe

Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Results posted on

2015-06-26

Participant Flow

Participants were recruited from ECOG member institutions between September 6, 2007 and May 7, 2010.

Participant milestones

Participant milestones
Measure	Arm A (VRD) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Overall Study STARTED	23	25
Overall Study Pts w/ Measurable Disease at Baseline	16	16
Overall Study Pts w/ QOL Assessments Complete	12	8
Overall Study COMPLETED	15	12
Overall Study NOT COMPLETED	8	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (VRD) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Overall Study Disease progression	0	3
Overall Study Adverse Event	7	7
Overall Study Withdrawal by Subject	1	1
Overall Study Physician Decision	0	1
Overall Study Non-compliance	0	1

Baseline Characteristics

Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (VRD) n=23 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) n=25 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO	Total n=48 Participants Total of all reporting groups
Age, Continuous	64 years n=93 Participants	65 years n=4 Participants	65 years n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	13 Participants n=4 Participants	21 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	12 Participants n=4 Participants	27 Participants n=27 Participants
Region of Enrollment United States	23 participants n=93 Participants	25 participants n=4 Participants	48 participants n=27 Participants

PRIMARY outcome

Timeframe: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Population: All randomized patients

Outcome measures

Outcome measures
Measure	Arm A (VRD) n=23 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) n=25 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Progression-free Survival (PFS)	NA Months Median PFS was not reached for Arm A (VRD).	17.4 Months Interval 7.1 to 35.4

SECONDARY outcome

Timeframe: Assessed at the end of each cycle, every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Population: Patients with measurable disease at randomization were included in this analysis.

CR: Patients with complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. To be considered CR, patients must meet all of the following criteria: * Negative immunofixation on the serum and urine at two consecutive times * Disappearance of any soft tissue plasmacytomas * ≤5% plasma cells in bone marrow * If serum and urine M protein are unmeasurable and the immunoglobulin free light chain (FLC) parameter is being used, patients must have a normal ratio of 0.26-1.65 at two consecutive times VGPR: * Serum and urine M-component detectable by immunofixation but not on electrophoresis OR * \>=90% reduction in serum M-component plus urine M-component \<100 mg per 24 hours (by SPEP and UPEP) * If the serum and urine M protein are unmeasurable and the immunoglobulin FLC parameter is being used, a \>90% decrease in the difference between involved and uninvolved FLC levels is required in place of the M protein criteria

Outcome measures

Outcome measures
Measure	Arm A (VRD) n=16 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) n=16 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR])	0.625 Proportion of patients Interval 0.354 to 0.848	0.188 Proportion of patients Interval 0.041 to 0.457

SECONDARY outcome

Population: All randomized patients

Overall survival is defined as the time from randomization to death or date of last known alive. The OS results are based on data as of April 2014.

Outcome measures

Outcome measures
Measure	Arm A (VRD) n=23 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) n=25 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Overall Survival (OS)	64.0 Months Interval 50.2 to 65.2	NA Months Median overall survival was not reached in Arm B.

SECONDARY outcome

Timeframe: Baseline and 6 months post consolidation treatment

Population: Patients with both assessments complete at baseline and 6 months post consolidation treatment were included in this analysis.

The combined score on the FACT-Ntx TOI is of interest. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible quality of life) -100 (best possible quality of life). The primary QOL endpoint is defined as the change in the FACT-Ntx TOI score from registration to 6 months post consolidation treatment.

Outcome measures

Outcome measures
Measure	Arm A (VRD) n=12 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Arm B (VD) n=8 Participants Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI)	-7.9 units on a scale Interval -43.0 to 20.0	-2.6 units on a scale Interval -20.0 to 20.0

Adverse Events

Arm A (VRd Regimen)

Serious events: 15 serious events

Other events: 8 other events

Deaths: 0 deaths

Arm B (Vd Regimen)

Serious events: 16 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm A (VRd Regimen) n=23 participants at risk Arm A (VRd Regimen) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin.	Arm B (Vd Regimen) n=25 participants at risk Arm B (Vd Regimen) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15.
Blood and lymphatic system disorders Hemoglobin	8.7% 2/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	16.0% 4/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Investigations Leukocytes	4.3% 1/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	8.0% 2/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Investigations Lymphopenia	4.3% 1/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	12.0% 3/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Investigations Neutrophils	0.00% 0/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	8.0% 2/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Investigations Platelets	4.3% 1/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	16.0% 4/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
General disorders Fatigue	13.0% 3/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	16.0% 4/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Psychiatric disorders Insomnia	13.0% 3/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	8.0% 2/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Skin and subcutaneous tissue disorders Rash/desquamation	8.7% 2/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	4.0% 1/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Gastrointestinal disorders Constipation	4.3% 1/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	8.0% 2/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Metabolism and nutrition disorders Hyperglycemia	8.7% 2/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	4.0% 1/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment
Nervous system disorders Neuropathy-sensory	17.4% 4/23 • Assessed every 21 days while on treatment and for 30 days after the end of treatment	16.0% 4/25 • Assessed every 21 days while on treatment and for 30 days after the end of treatment

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60