Trial Outcomes & Findings for Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma (NCT NCT00477750)
NCT ID: NCT00477750
Last Updated: 2019-10-11
Results Overview
Response that was confirmed on 2 consecutive evaluations.\> * Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and \<=5% plasma cells in bone marrow\> * Very Good Partial Response (VGPR): \>=90% reduction in serum M-spike, Urine M-spike \<100mg per 24 hours\> * Partial Response (PR): \>=50% reduction in serum M-spike, Urine M-spike \>=90% reduction or \< 200mg per 24 hours, or \>=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells
COMPLETED
PHASE1/PHASE2
33 participants
Every cycle during treatment
2019-10-11
Participant Flow
This was as Phase I/II trial. There were 7 patients recruited to the Phase I portion; no patients qualified for the Phase II portion. Twenty-six (26) patients were recruited for the Phase II portion. Results presented here are on the 26 Phase II patients.
Participant milestones
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression
Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression
Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression
Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression
Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Overall Study
Currently Receiving Treatment
|
11
|
Baseline Characteristics
Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=26 Participants
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression
Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression
Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Age, Continuous
|
73.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=5 Participants
|
|
Durie-Salmon Stage at Diagnosis
I - Low Cell Mass
|
1 participants
n=5 Participants
|
|
Durie-Salmon Stage at Diagnosis
II - Intermediate Cell Mass
|
11 participants
n=5 Participants
|
|
Durie-Salmon Stage at Diagnosis
III - High Cell Mass
|
11 participants
n=5 Participants
|
|
Durie-Salmon Stage at Diagnosis
unknown
|
3 participants
n=5 Participants
|
|
Parameter of Hematologic Response - Serum M-spike >= 1g/dL
Yes
|
20 participants
n=5 Participants
|
|
Parameter of Hematologic Response - Serum M-spike >= 1g/dL
No
|
6 participants
n=5 Participants
|
|
Parameter of Hematologic Response - Serum Immunoglobulin Free Light Chain >= 10mg/dL
Yes
|
12 participants
n=5 Participants
|
|
Parameter of Hematologic Response - Serum Immunoglobulin Free Light Chain >= 10mg/dL
No
|
14 participants
n=5 Participants
|
|
Parameter of Hematologic Response - Urine M-spike >= 200 mg/24 hours
Yes
|
6 participants
n=5 Participants
|
|
Parameter of Hematologic Response - Urine M-spike >= 200 mg/24 hours
No
|
20 participants
n=5 Participants
|
|
Parameter of Hematologic Response - None (non-secretory myeloma, bone marrow only)
Yes
|
0 participants
n=5 Participants
|
|
Parameter of Hematologic Response - None (non-secretory myeloma, bone marrow only)
No
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every cycle during treatmentResponse that was confirmed on 2 consecutive evaluations.\> * Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and \<=5% plasma cells in bone marrow\> * Very Good Partial Response (VGPR): \>=90% reduction in serum M-spike, Urine M-spike \<100mg per 24 hours\> * Partial Response (PR): \>=50% reduction in serum M-spike, Urine M-spike \>=90% reduction or \< 200mg per 24 hours, or \>=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells
Outcome measures
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=26 Participants
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression\> \> Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression\>
\> Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Patients With Overall Confirmed Response
CR
|
3 participants
|
|
Patients With Overall Confirmed Response
VGPR
|
5 participants
|
|
Patients With Overall Confirmed Response
PR
|
10 participants
|
SECONDARY outcome
Timeframe: registration to progressive disease (up to 3 years)Population: Phase 2 patients
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. 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 |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=26 Participants
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression\> \> Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression\>
\> Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Progression-free Survival
|
21.4 months
Interval 15.3 to 23.5
|
SECONDARY outcome
Timeframe: registration to death (up to 3 years)Population: Phase 2 patients.
OS was defined as the time from registration to death due to any cause. Patients who were alive were censored at date of last follow-up. The overall survival at 3 years (a percentage) is reported below.
Outcome measures
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=26 Participants
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression\> \> Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression\>
\> Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Overall Survival (OS) at 3 Years
|
58 percentage of patients
Interval 42.0 to 80.0
|
SECONDARY outcome
Timeframe: from first response to progression or death (up to 3 years)Population: Phase 2 Patients who had a response of PR or better are included in this analysis.
Duration of response was calculated from documentation of first response to date of progression in the subset of patients who responded. Patients without progression were censored at the date of last tumor evaluation.
Outcome measures
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=18 Participants
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression\> \> Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression\>
\> Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Duration of Response (DOR)
|
16.3 months
Interval 14.3 to 26.4
|
SECONDARY outcome
Timeframe: Every cycle during treatment up to 3 yearsPopulation: Patients who experienced an adverse event that is at least possibly related are included in this analysis.
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Outcome measures
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=3 Participants
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression\> \> Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression\>
\> Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
Grade 3
|
33 percentage of patients
|
|
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
Grade 4
|
67 percentage of patients
|
|
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
Grade 5
|
0 percentage of patients
|
Adverse Events
Treatment (Lenalidomide, Melphalan, Prednisone)
Serious adverse events
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=26 participants at risk
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression
Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression
Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Sepsis
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Skin infection
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Creatinine increased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
7.7%
2/26 • Number of events 2
|
|
Investigations
Platelet count decreased
|
7.7%
2/26 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
3.8%
1/26 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
3.8%
1/26 • Number of events 1
|
Other adverse events
| Measure |
Treatment (Lenalidomide, Melphalan, Prednisone)
n=26 participants at risk
Intervention: Drug: lenalidomide 10 mg orally days 1-21 every 28 days until progression
Intervention: Drug: melphalan 5mg/m\^2 orally days 1-4 every 28 days until progression
Intervention: Drug: prednisone 60mg/m\^2, orally days 1-4 every 28 days until progression
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
92.3%
24/26 • Number of events 103
|
|
Blood and lymphatic system disorders
Lymphatic disorder
|
3.8%
1/26 • Number of events 1
|
|
Cardiac disorders
Myocardial ischemia
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
3.8%
1/26 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
15.4%
4/26 • Number of events 5
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
7.7%
2/26 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
30.8%
8/26 • Number of events 12
|
|
General disorders
Edema limbs
|
42.3%
11/26 • Number of events 27
|
|
General disorders
Fatigue
|
80.8%
21/26 • Number of events 63
|
|
General disorders
Fever
|
3.8%
1/26 • Number of events 1
|
|
General disorders
Pain
|
7.7%
2/26 • Number of events 5
|
|
Immune system disorders
Hypersensitivity
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Skin infection
|
7.7%
2/26 • Number of events 5
|
|
Infections and infestations
Upper respiratory infection
|
3.8%
1/26 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Alkaline phosphatase increased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
23.1%
6/26 • Number of events 13
|
|
Investigations
Lymphocyte count decreased
|
3.8%
1/26 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
69.2%
18/26 • Number of events 58
|
|
Investigations
Platelet count decreased
|
69.2%
18/26 • Number of events 70
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
57.7%
15/26 • Number of events 32
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
3.8%
1/26 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
3.8%
1/26 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum glucose decreased
|
3.8%
1/26 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
3.8%
1/26 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
34.6%
9/26 • Number of events 17
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Headache
|
3.8%
1/26 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
19.2%
5/26 • Number of events 8
|
|
Nervous system disorders
Syncope
|
7.7%
2/26 • Number of events 2
|
|
Psychiatric disorders
Confusion
|
3.8%
1/26 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
23.1%
6/26 • Number of events 14
|
|
Vascular disorders
Hypotension
|
3.8%
1/26 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place