Trial Outcomes & Findings for A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis (NCT NCT00890552)
NCT ID: NCT00890552
Last Updated: 2017-03-22
Results Overview
At the end of each treatment cycle (4 weeks), hematologic response rate as assessed. Hematologic response was considered to be amyloid complete response (normal FLC ratio and negative serum and urine immunofixation); very good partial response (difference between involved and uninvolved FLCs \[dFLC\] \< 40 mg/L); or partial response (dFLC decrease \> 50%).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
25 participants
Primary outcome timeframe
8 weeks
Results posted on
2017-03-22
Participant Flow
Participant milestones
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.
Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.
Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.
|
|---|---|
|
Enrollment and Pre-treatment
STARTED
|
25
|
|
Enrollment and Pre-treatment
COMPLETED
|
24
|
|
Enrollment and Pre-treatment
NOT COMPLETED
|
1
|
|
On-treatment
STARTED
|
24
|
|
On-treatment
COMPLETED
|
14
|
|
On-treatment
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.
Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.
Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.
|
|---|---|
|
Enrollment and Pre-treatment
Death/ lost to follow up
|
1
|
|
On-treatment
Early prog disease/ death
|
10
|
Baseline Characteristics
A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis
Baseline characteristics by cohort
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=25 Participants
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
|
|---|---|
|
Age, Continuous
|
67 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
ECOG Performance Status (PS)
ECOG PS 1
|
12 participants
n=5 Participants
|
|
ECOG Performance Status (PS)
ECOG PS 2
|
9 participants
n=5 Participants
|
|
ECOG Performance Status (PS)
ECOG PS 3
|
4 participants
n=5 Participants
|
|
Hematologic disease burden
Kappa free light chain (%)
|
20 Percentage of participants
n=5 Participants
|
|
Hematologic disease burden
Lambda free light chain (%)
|
80 Percentage of participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Subjects completing at least one full cycle of study treatment
At the end of each treatment cycle (4 weeks), hematologic response rate as assessed. Hematologic response was considered to be amyloid complete response (normal FLC ratio and negative serum and urine immunofixation); very good partial response (difference between involved and uninvolved FLCs \[dFLC\] \< 40 mg/L); or partial response (dFLC decrease \> 50%).
Outcome measures
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=24 Participants
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.
Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.
Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.
|
|---|---|
|
Hematologic Response Rate
Complete Response (CR)
|
2 participants
|
|
Hematologic Response Rate
Very good Partial Response (VGPR)
|
4 participants
|
|
Hematologic Response Rate
Partial Response (PR)
|
8 participants
|
|
Hematologic Response Rate
No Response (NR)
|
9 participants
|
|
Hematologic Response Rate
Response not evaluable
|
1 participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All subjects receiving MDR treatment.
Participants alive 12 months after starting MDR treatment.
Outcome measures
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=24 Participants
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.
Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.
Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.
|
|---|---|
|
Overall Survival (OS)
|
58 percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All participants starting MDR treatment
Assessed as the median value for EFS 12 months after starting MDR treatment
Outcome measures
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=14 Participants
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.
Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.
Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.
|
|---|---|
|
Event-free Survival (EFS)
|
3.15 months
Interval 0.25 to 12.0
|
SECONDARY outcome
Timeframe: 32 monthsPopulation: All participants who achieved at least a partial response (9 subjects were not included due to not having any response)
Assessed as the median value for the time from first partial response until progression; death; or last follow-up.
Outcome measures
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=14 Participants
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.
Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.
Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.
|
|---|---|
|
Duration of Response
|
9.1 months
Interval 0.0 to 31.25
|
Adverse Events
Lenalidomide, Melphalan and Dexamethasone (MDR)
Serious events: 19 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=25 participants at risk
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
|
|---|---|
|
Cardiac disorders
Atrial fibrillation
|
16.0%
4/25 • 12 months
|
|
Infections and infestations
Febrile neutropenia
|
4.0%
1/25 • 12 months
|
|
Gastrointestinal disorders
Hemorrhage
|
8.0%
2/25 • 12 months
|
|
General disorders
Death
|
28.0%
7/25 • 12 months
|
|
Gastrointestinal disorders
Dehydration
|
8.0%
2/25 • 12 months
|
|
General disorders
Syncope
|
16.0%
4/25 • 12 months
|
|
Blood and lymphatic system disorders
Anemia in Neoplastic disease
|
4.0%
1/25 • 12 months
|
|
Metabolism and nutrition disorders
Primary Amyloidosis
|
4.0%
1/25 • 12 months
|
|
Gastrointestinal disorders
Constipation
|
4.0%
1/25 • 12 months
|
|
Psychiatric disorders
Altered mental status
|
4.0%
1/25 • 12 months
|
|
Cardiac disorders
Ventricular tachycardia
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Edema
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Hypoglycemia
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Hypovolemia
|
4.0%
1/25 • 12 months
|
|
Metabolism and nutrition disorders
Renal failure
|
4.0%
1/25 • 12 months
|
|
Infections and infestations
Pneumonia
|
4.0%
1/25 • 12 months
|
|
Cardiac disorders
Atrial flutter
|
4.0%
1/25 • 12 months
|
|
Cardiac disorders
Bradycardia
|
4.0%
1/25 • 12 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
12.0%
3/25 • 12 months
|
Other adverse events
| Measure |
Lenalidomide, Melphalan and Dexamethasone (MDR)
n=25 participants at risk
The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
|
|---|---|
|
Gastrointestinal disorders
Anorexia
|
16.0%
4/25 • 12 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
8.0%
2/25 • 12 months
|
|
Blood and lymphatic system disorders
Bone and Blood Marrow
|
20.0%
5/25 • 12 months
|
|
Blood and lymphatic system disorders
Hypocalcemia
|
12.0%
3/25 • 12 months
|
|
Gastrointestinal disorders
Constipation
|
24.0%
6/25 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.0%
2/25 • 12 months
|
|
Metabolism and nutrition disorders
Creatinine
|
12.0%
3/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Dermatology
|
8.0%
2/25 • 12 months
|
|
Gastrointestinal disorders
Diarrhea
|
20.0%
5/25 • 12 months
|
|
Gastrointestinal disorders
Distension/bloating
|
12.0%
3/25 • 12 months
|
|
Nervous system disorders
Dizziness
|
28.0%
7/25 • 12 months
|
|
Gastrointestinal disorders
Dry mouth
|
12.0%
3/25 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysphagia
|
40.0%
10/25 • 12 months
|
|
Infections and infestations
Edema: limbs
|
44.0%
11/25 • 12 months
|
|
General disorders
Fatigue
|
64.0%
16/25 • 12 months
|
|
General disorders
Fever
|
20.0%
5/25 • 12 months
|
|
Gastrointestinal disorders
Gastrointestinal
|
32.0%
8/25 • 12 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.0%
3/25 • 12 months
|
|
Hepatobiliary disorders
Hematoma
|
8.0%
2/25 • 12 months
|
|
Hepatobiliary disorders
Hemoglobin
|
8.0%
2/25 • 12 months
|
|
Blood and lymphatic system disorders
Hemolysis
|
24.0%
6/25 • 12 months
|
|
Cardiac disorders
Hypotension
|
12.0%
3/25 • 12 months
|
|
Infections and infestations
Infection
|
44.0%
11/25 • 12 months
|
|
Blood and lymphatic system disorders
INR
|
8.0%
2/25 • 12 months
|
|
General disorders
Insomnia
|
16.0%
4/25 • 12 months
|
|
Blood and lymphatic system disorders
Leukocytes
|
8.0%
2/25 • 12 months
|
|
General disorders
Mood alteration- Anxiety
|
12.0%
3/25 • 12 months
|
|
Gastrointestinal disorders
Nausea
|
12.0%
3/25 • 12 months
|
|
Nervous system disorders
Neuropathy: sensory
|
24.0%
6/25 • 12 months
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes
|
16.0%
4/25 • 12 months
|
|
General disorders
Pain
|
48.0%
12/25 • 12 months
|
|
Blood and lymphatic system disorders
Platelets
|
72.0%
18/25 • 12 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.0%
4/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
44.0%
11/25 • 12 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
20.0%
5/25 • 12 months
|
|
Cardiac disorders
Thrombotic microangiopathy
|
8.0%
2/25 • 12 months
|
|
Eye disorders
Vision-blurred
|
8.0%
2/25 • 12 months
|
|
Gastrointestinal disorders
Vomitting
|
8.0%
2/25 • 12 months
|
|
Gastrointestinal disorders
weight loss
|
20.0%
5/25 • 12 months
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
4.0%
1/25 • 12 months
|
|
Gastrointestinal disorders
Ascites (non-malignant)
|
4.0%
1/25 • 12 months
|
|
Metabolism and nutrition disorders
AST, SGOT
|
4.0%
1/25 • 12 months
|
|
Ear and labyrinth disorders
Auditory/Ear
|
4.0%
1/25 • 12 months
|
|
Metabolism and nutrition disorders
Hyperbilirubinemia
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Coagulation
|
4.0%
1/25 • 12 months
|
|
Renal and urinary disorders
Cystitis
|
4.0%
1/25 • 12 months
|
|
General disorders
Dehydration
|
4.0%
1/25 • 12 months
|
|
Infections and infestations
abscess
|
4.0%
1/25 • 12 months
|
|
Eye disorders
Dry eye syndrome
|
4.0%
1/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.0%
1/25 • 12 months
|
|
Gastrointestinal disorders
Dysphagia
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Edema: head and neck
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Edema: trunk/genital
|
4.0%
1/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
4.0%
1/25 • 12 months
|
|
Ear and labyrinth disorders
Hearing loss
|
4.0%
1/25 • 12 months
|
|
Blood and lymphatic system disorders
Lymphatics
|
4.0%
1/25 • 12 months
|
|
Psychiatric disorders
Depression
|
4.0%
1/25 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
8.0%
2/25 • 12 months
|
|
Nervous system disorders
Neuropathy: motor
|
4.0%
1/25 • 12 months
|
|
Eye disorders
Ocular/Visual
|
4.0%
1/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Petechiae/purpura
|
4.0%
1/25 • 12 months
|
|
Renal and urinary disorders
Dysuria
|
4.0%
1/25 • 12 months
|
|
General disorders
Rigors/chills
|
4.0%
1/25 • 12 months
|
|
Cardiac disorders
Sinus arrhythmia
|
8.0%
2/25 • 12 months
|
|
Cardiac disorders
Sinus bradycardia
|
4.0%
1/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Sweating
|
4.0%
1/25 • 12 months
|
|
General disorders
dysarthria
|
4.0%
1/25 • 12 months
|
|
Skin and subcutaneous tissue disorders
Wound complication
|
4.0%
1/25 • 12 months
|
Additional Information
Brenda Hann, RN, MBA, CCRC
Stanford University School of Medicine
Phone: 650-723-0966
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place