Trial Outcomes & Findings for Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma (NCT NCT00772915)

NCT ID: NCT00772915

Last Updated: 2020-01-18

Results Overview

PFS rate at 12 months is defined as the percentage of participants who are alive and progression-free at 12 months. Progression is exclusively defined as a patient with progressive disease while receiving treatment with lenalidomide in combination with dexamethasone. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in: * Serum M-component (absolute increase \>= 0.5g/dl) * Urine M-component (absolute increase \>= 200mg/24hour * Difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl * Bone marrow plasma cell percentage (absolute increase of \>=10%)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 39 participants
• Primary outcome timeframe: 12 months from registration
• Results posted on: 2020-01-18

Participant Flow

Thirty-nine (39) participants were recruited at Mayo Clinic (Rochester) between December 2008 and April 2010.

One participant canceled prior to starting treatment; this participant has been removed from all analyses.

Participant milestones

Measure	Lenalidomide With On-Demand Dexamethasone Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Overall Study STARTED	38
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Baseline characteristics by cohort

Measure	Lenalidomide With On-Demand Dexamethasone n=38 Participants Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Age, Continuous	66 years n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Region of Enrollment United States	38 participants n=5 Participants
Durie Salmon Stage at Diagnosis Stage I: Low Cell Mass	8 participants n=5 Participants
Durie Salmon Stage at Diagnosis Stage II: Intermediate Cell Mass	15 participants n=5 Participants
Durie Salmon Stage at Diagnosis Stage III: High Cell Mass	12 participants n=5 Participants
Durie Salmon Stage at Diagnosis Not Assessed	3 participants n=5 Participants
Parameter of Hematologic Response: Serum M-Spike >= 1 mg/dL Yes	26 participants n=5 Participants
Parameter of Hematologic Response: Serum M-Spike >= 1 mg/dL No	12 participants n=5 Participants
Parameter of Hematologic Response: Serum Immunoglobulin Free Light Chain >= 10 mg/dL Yes	25 participants n=5 Participants
Parameter of Hematologic Response: Serum Immunoglobulin Free Light Chain >= 10 mg/dL No	13 participants n=5 Participants
Parameter of Hematologic Response: Urine M-Spike >= 200 mg/24 hours Yes	14 participants n=5 Participants
Parameter of Hematologic Response: Urine M-Spike >= 200 mg/24 hours No	24 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months from registration

PFS rate at 12 months is defined as the percentage of participants who are alive and progression-free at 12 months. Progression is exclusively defined as a patient with progressive disease while receiving treatment with lenalidomide in combination with dexamethasone. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in:

• Serum M-component (absolute increase >= 0.5g/dl)
• Urine M-component (absolute increase >= 200mg/24hour
• Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl
• Bone marrow plasma cell percentage (absolute increase of >=10%)

Outcome measures

Measure	Lenalidomide With On-Demand Dexamethasone n=38 Participants Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Progression-free Survival (PFS) Rate at 12 Months	79 percentage of participants Interval 65.0 to 96.0

SECONDARY outcome

Timeframe: Up to 18 cycles from registration

Confirmed response rate is defined as the percentage of participants who achieved a response that was confirmed on 2 consecutive evaluations during treatment

• Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM)
• Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM
• Partial Response PR): >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels

Outcome measures

Measure	Lenalidomide With On-Demand Dexamethasone n=38 Participants Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Confirmed Response Rate	61 percentage of participants Interval 43.0 to 76.0

SECONDARY outcome

Timeframe: Time from registration to death (up to 3 years)

OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 3 years from randomization. The median OS with 95% CI was estimated using the Kaplan Meier method

Outcome measures

Measure	Lenalidomide With On-Demand Dexamethasone n=38 Participants Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Overall Survival (OS)	61.1 months Interval 26.0 to 75.0

SECONDARY outcome

Timeframe: Time from registration to progression or death (up to 3 years)

PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.

Progression was defined as any one or more of the following:An increase of 25% from lowest confirmed response in:

• Serum M-component (absolute increase >= 0.5g/dl)
• Urine M-component (absolute increase >= 200mg/24hour
• Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl
• Bone marrow plasma cell percentage (absolute increase of >=10%)

Outcome measures

Measure	Lenalidomide With On-Demand Dexamethasone n=38 Participants Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Progression-free Survival (PFS)	27 months Interval 13.7 to 75.0

SECONDARY outcome

Timeframe: Duration on treatment (up to 18 cycles from registration)

The number of participants who experienced toxicity (defined as at least one grade 3 or higher adverse event at least possibly related to treatment) is reported below.

Outcome measures

Measure	Lenalidomide With On-Demand Dexamethasone n=38 Participants Lenalidomide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity)	23 Participants

Adverse Events

Lenalidomide With On-Demand Dexamethasone

Serious events: 9 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lenalidomide With On-Demand Dexamethasone n=38 participants at risk Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Cardiac disorders Left ventricular failure	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Dysphagia	2.6% 1/38 • Number of events 1
General disorders Chills	2.6% 1/38 • Number of events 1
General disorders Fatigue	2.6% 1/38 • Number of events 1
Infections and infestations Meningitis	2.6% 1/38 • Number of events 1
Infections and infestations Pneumonia	2.6% 1/38 • Number of events 1
Infections and infestations Sepsis	2.6% 1/38 • Number of events 1
Injury, poisoning and procedural complications Fracture	2.6% 1/38 • Number of events 1
Injury, poisoning and procedural complications Intraoperative musculoskeletal injury	2.6% 1/38 • Number of events 1
Investigations Neutrophil count decreased	2.6% 1/38 • Number of events 1
Renal and urinary disorders Renal Failure	2.6% 1/38 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.6% 1/38 • Number of events 1
Vascular disorders Thrombosis	5.3% 2/38 • Number of events 2

Other adverse events

Measure	Lenalidomide With On-Demand Dexamethasone n=38 participants at risk Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, \& 22) orally with food until progression.
Blood and lymphatic system disorders Anemia	94.7% 36/38 • Number of events 311
Eye disorders Cataract	2.6% 1/38 • Number of events 2
Gastrointestinal disorders Colitis	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Constipation	7.9% 3/38 • Number of events 9
Gastrointestinal disorders Diarrhea	7.9% 3/38 • Number of events 4
Gastrointestinal disorders Gastrointestinal	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Mucositis oral	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Nausea	2.6% 1/38 • Number of events 2
General disorders Fatigue	89.5% 34/38 • Number of events 258
General disorders Pain	2.6% 1/38 • Number of events 1
General disorders Pain-Chest	5.3% 2/38 • Number of events 2
Infections and infestations Gallbladder (cholecystitis) infection	2.6% 1/38 • Number of events 1
Infections and infestations Infection without neutropenia	2.6% 1/38 • Number of events 1
Infections and infestations Pneumonia	2.6% 1/38 • Number of events 2
Infections and infestations Skin (cellulites) infection	5.3% 2/38 • Number of events 2
Infections and infestations Upper airway infection	7.9% 3/38 • Number of events 5
Injury, poisoning and procedural complications Fracture	2.6% 1/38 • Number of events 1
Investigations Alanine aminotransferase increased	2.6% 1/38 • Number of events 1
Investigations Aspartate aminotransferase increased	2.6% 1/38 • Number of events 3
Investigations Bilirubin	5.3% 2/38 • Number of events 4
Investigations Creatinine increased	2.6% 1/38 • Number of events 1
Investigations Leukopenia	86.8% 33/38 • Number of events 174
Investigations Lymphocyte count decreased	7.9% 3/38 • Number of events 12
Investigations Neutrophil count decreased	81.6% 31/38 • Number of events 171
Investigations Platelet count decreased	50.0% 19/38 • Number of events 108
Investigations Weight gain	2.6% 1/38 • Number of events 1
Metabolism and nutrition disorders Dehydration	2.6% 1/38 • Number of events 1
Metabolism and nutrition disorders Hypercalcemia	2.6% 1/38 • Number of events 1
Metabolism and nutrition disorders Hyperglycemia	10.5% 4/38 • Number of events 8
Metabolism and nutrition disorders Hypocalcemia	2.6% 1/38 • Number of events 1
Metabolism and nutrition disorders Hypoglycemia	5.3% 2/38 • Number of events 2
Musculoskeletal and connective tissue disorders Arthralgia	2.6% 1/38 • Number of events 4
Musculoskeletal and connective tissue disorders Back pain	5.3% 2/38 • Number of events 3
Musculoskeletal and connective tissue disorders Bone pain	2.6% 1/38 • Number of events 1
Musculoskeletal and connective tissue disorders Neck pain	2.6% 1/38 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	60.5% 23/38 • Number of events 150
Nervous system disorders Syncope	2.6% 1/38 • Number of events 1
Nervous system disorders Tremor	2.6% 1/38 • Number of events 3
Psychiatric disorders Depression	2.6% 1/38 • Number of events 8
Psychiatric disorders Insomnia	7.9% 3/38 • Number of events 3
Renal and urinary disorders Renal Failure	2.6% 1/38 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	2.6% 1/38 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/38 • Number of events 1
Skin and subcutaneous tissue disorders Erythema multiforme	2.6% 1/38 • Number of events 1
Skin and subcutaneous tissue disorders Pruritus	2.6% 1/38 • Number of events 1
Skin and subcutaneous tissue disorders Rash	7.9% 3/38 • Number of events 3
Vascular disorders Hot flashes	2.6% 1/38 • Number of events 2
Vascular disorders Phlebitis	2.6% 1/38 • Number of events 1
Vascular disorders Thrombosis	2.6% 1/38 • Number of events 1

Additional Information

Dr. Shaji Kumar

Mayo Clinic

Email: kumar.shaji@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place