Trial Outcomes & Findings for Lenalidomide for Myelodysplastic Syndrome Refractory to Hypomethylating Agents (NCT NCT01246076)
NCT ID: NCT01246076
Last Updated: 2016-01-05
Results Overview
* Complete remission (CR): ≤5% myeloblasts bone marrow blasts, normal maturation in all cell lines (dysplasia will be noted), ≥11 g/dl peripheral blood hemoglobin, ≥100x10\^9cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood absolute neutrophil count (ANC), and 0% peripheral blood blasts. * Marrow complete remission (MCR): ≤5% myeloblasts and decreased by ≥50% compared to pre-treatment bone marrow blasts, bone marrow morphology not relevant, and peripheral blood (if hematological improvement they will be noted in addition to marrow CR). * Partial remission (PR): previously had ≥5% myeloblasts and now have ≥5% myeloblasts but decreased by ≥50% compared to pre-treatment, bone marrow morphology not relevant, ≥11 g/dl peripheral blood hemoglobin, ≥100x109cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood ANC, and 0% peripheral blood blasts
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
Up to 56 weeks (14 cycles of treatment)
Results posted on
2016-01-05
Participant Flow
The study opened to participant enrollment on 06/30/2011 and closed to participant enrollment on 05/19/2014.
Participant milestones
| Measure |
Lenalidomide
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lenalidomide for Myelodysplastic Syndrome Refractory to Hypomethylating Agents
Baseline characteristics by cohort
| Measure |
Lenalidomide
n=24 Participants
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Age, Continuous
|
73 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 56 weeks (14 cycles of treatment)Population: 8 participants were not evaluable for this outcome measure because they did not complete at least one cycle of therapy.
* Complete remission (CR): ≤5% myeloblasts bone marrow blasts, normal maturation in all cell lines (dysplasia will be noted), ≥11 g/dl peripheral blood hemoglobin, ≥100x10\^9cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood absolute neutrophil count (ANC), and 0% peripheral blood blasts. * Marrow complete remission (MCR): ≤5% myeloblasts and decreased by ≥50% compared to pre-treatment bone marrow blasts, bone marrow morphology not relevant, and peripheral blood (if hematological improvement they will be noted in addition to marrow CR). * Partial remission (PR): previously had ≥5% myeloblasts and now have ≥5% myeloblasts but decreased by ≥50% compared to pre-treatment, bone marrow morphology not relevant, ≥11 g/dl peripheral blood hemoglobin, ≥100x109cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood ANC, and 0% peripheral blood blasts
Outcome measures
| Measure |
Lenalidomide
n=16 Participants
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria
CR
|
0 participants
|
|
Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria
MCR
|
8 participants
|
|
Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria
PR
|
0 participants
|
|
Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria
HI
|
2 participants
|
SECONDARY outcome
Timeframe: 6 months after end of treatment (up to 82 weeks from start of treatment)-Overall survival rate is the percentage of participants who were alive 6 months after end of treatment.
Outcome measures
| Measure |
Lenalidomide
n=24 Participants
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Overall Survival Rate
|
29 percentage of participants
|
SECONDARY outcome
Timeframe: Until 6 months after end of treatmentPopulation: 8 participants had a response -- all had MCR.
Outcome measures
| Measure |
Lenalidomide
n=8 Participants
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Duration of Response
|
70 days
Interval 28.0 to 336.0
|
SECONDARY outcome
Timeframe: Up to 56 weeks (14 cycles)Population: 16 out of 24 participants were evaluable for this outcome measure as these 16 participants completed at least the first cycle of treatment.
Outcome measures
| Measure |
Lenalidomide
n=16 Participants
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Time to Discontinuation of Treatment
|
2 cycles
Interval 1.0 to 12.0
|
SECONDARY outcome
Timeframe: 30 days after end of treatment (up to 60 weeks)Outcome measures
| Measure |
Lenalidomide
n=24 Participants
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
Pneumonia
|
12 participants
|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
Sepsis
|
4 participants
|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
Febrile neutropenia
|
8 participants
|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
Rash
|
2 participants
|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
Thromboembolic event
|
1 participants
|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
Myocardial infarction
|
1 participants
|
|
Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4
New cancer - mammary analogue salivary carcinoma
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 6 months after completion of treatment (up to 82 weeks from start of treatment)Population: Time to progression was not analyzed. This was a prespecified secondary outcome but due to the early termination of the study time to progression was not followed.
The time to progression is defined as the time from registration to the date of progression or last follow-up. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred.
Outcome measures
Outcome data not reported
Adverse Events
Lenalidomide
Serious events: 19 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lenalidomide
n=24 participants at risk
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
4.2%
1/24
|
|
Blood and lymphatic system disorders
Anemia
|
4.2%
1/24
|
|
Cardiac disorders
Cardiac arrest
|
4.2%
1/24
|
|
General disorders
Death
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Dehydration
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.2%
1/24
|
|
Injury, poisoning and procedural complications
Fall
|
4.2%
1/24
|
|
Infections and infestations
Febrile neutropenia
|
20.8%
5/24
|
|
Vascular disorders
Hematoma
|
4.2%
1/24
|
|
Renal and urinary disorders
Hematuria
|
4.2%
1/24
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
High grade adenocarcinoma
|
4.2%
1/24
|
|
Infections and infestations
Lung infection
|
33.3%
8/24
|
|
Investigations
Platelet count decreased
|
4.2%
1/24
|
|
Infections and infestations
Sepsis
|
12.5%
3/24
|
|
Infections and infestations
Skin infection
|
4.2%
1/24
|
|
Vascular disorders
Thromboembolic event: pulmonary embolism
|
4.2%
1/24
|
|
Investigations
White blood cell decreased
|
4.2%
1/24
|
Other adverse events
| Measure |
Lenalidomide
n=24 participants at risk
Lenalidomide 50 mg/day for two 28 day cycles.
Patients who have bone marrow aplasia as defined by a cellularity of \<10% will be observed till counts recover. If patients do not progress following 2 cycles of HD lenalidomide, they will receive low dose lenalidomide 10 mg daily for 12 cycles.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
3/24
|
|
Investigations
Activated partial thromboplastin time prolonged
|
29.2%
7/24
|
|
Renal and urinary disorders
Acute kidney injury
|
16.7%
4/24
|
|
Nervous system disorders
Akathisia
|
4.2%
1/24
|
|
Investigations
Alanine aminotransferase increased
|
54.2%
13/24
|
|
Investigations
Alkaline phosphatase increased
|
33.3%
8/24
|
|
Immune system disorders
Allergic reaction
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.3%
2/24
|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
8/24
|
|
Metabolism and nutrition disorders
Anorexia
|
29.2%
7/24
|
|
Psychiatric disorders
Anxiety
|
20.8%
5/24
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.2%
1/24
|
|
Investigations
Aspartate aminotransferase increased
|
45.8%
11/24
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
12.5%
3/24
|
|
Cardiac disorders
Atrial fibrillation
|
16.7%
4/24
|
|
Immune system disorders
Autoimmune hemolytic anemia
|
4.2%
1/24
|
|
Investigations
BUN increased
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
6/24
|
|
Investigations
Blood bilirubin increased
|
41.7%
10/24
|
|
Infections and infestations
Blood-Enterococcus faecium
|
4.2%
1/24
|
|
Eye disorders
Blurred vision
|
8.3%
2/24
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
12.5%
3/24
|
|
Injury, poisoning and procedural complications
Bruising
|
45.8%
11/24
|
|
Skin and subcutaneous tissue disorders
Bullous dermatitis
|
4.2%
1/24
|
|
Investigations
Cardiac troponin I increased
|
8.3%
2/24
|
|
Cardiac disorders
Chest pain
|
4.2%
1/24
|
|
Investigations
Chills
|
20.8%
5/24
|
|
Infections and infestations
Clostridium difficile infection
|
8.3%
2/24
|
|
Psychiatric disorders
Confusion
|
16.7%
4/24
|
|
Gastrointestinal disorders
Constipation
|
37.5%
9/24
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
41.7%
10/24
|
|
Investigations
Creatinine increased
|
29.2%
7/24
|
|
Metabolism and nutrition disorders
Dehydration
|
20.8%
5/24
|
|
Gastrointestinal disorders
Dental carries
|
8.3%
2/24
|
|
Psychiatric disorders
Depression
|
4.2%
1/24
|
|
Gastrointestinal disorders
Diarrhea
|
41.7%
10/24
|
|
Cardiac disorders
Diastolic dysfunction
|
4.2%
1/24
|
|
Nervous system disorders
Dizziness
|
41.7%
10/24
|
|
Gastrointestinal disorders
Dry mouth
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
4/24
|
|
Nervous system disorders
Dysgeusia
|
8.3%
2/24
|
|
Gastrointestinal disorders
Dyspepsia
|
12.5%
3/24
|
|
Gastrointestinal disorders
Dysphagia
|
12.5%
3/24
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
62.5%
15/24
|
|
Ear and labyrinth disorders
Ear pain
|
4.2%
1/24
|
|
General disorders
Edema face
|
4.2%
1/24
|
|
General disorders
Edema limbs
|
4.2%
1/24
|
|
Investigations
Ejection fraction decreased
|
4.2%
1/24
|
|
Cardiac disorders
Ejection fraction decreased
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
33.3%
8/24
|
|
Injury, poisoning and procedural complications
Fall
|
8.3%
2/24
|
|
General disorders
Fatigue
|
70.8%
17/24
|
|
Infections and infestations
Febrile neutropenia
|
12.5%
3/24
|
|
General disorders
Fever
|
25.0%
6/24
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
4.2%
1/24
|
|
General disorders
Fluid overload
|
4.2%
1/24
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Generalized aches and pains
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
29.2%
7/24
|
|
Psychiatric disorders
Hallucinations
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Hand cramps
|
4.2%
1/24
|
|
Nervous system disorders
Headache
|
29.2%
7/24
|
|
Ear and labyrinth disorders
Hearing impaired
|
4.2%
1/24
|
|
Vascular disorders
Hematoma
|
8.3%
2/24
|
|
Renal and urinary disorders
Hematuria
|
4.2%
1/24
|
|
Infections and infestations
Herpes stomatitis
|
4.2%
1/24
|
|
Injury, poisoning and procedural complications
Hip fracture
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
12.5%
3/24
|
|
Vascular disorders
Hot flashes
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
16.7%
4/24
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hypernatremia
|
12.5%
3/24
|
|
Vascular disorders
Hypertension
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
70.8%
17/24
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
66.7%
16/24
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
8/24
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
Hyponatremia
|
41.7%
10/24
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
29.2%
7/24
|
|
Vascular disorders
Hypotension
|
25.0%
6/24
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
25.0%
6/24
|
|
Investigations
INR increased
|
33.3%
8/24
|
|
Psychiatric disorders
Insomnia
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
Iron overload
|
4.2%
1/24
|
|
Nervous system disorders
Lethargy
|
8.3%
2/24
|
|
General disorders
Localized edema
|
4.2%
1/24
|
|
Infections and infestations
Lung infection
|
16.7%
4/24
|
|
Investigations
Lymphocyte count decreased
|
54.2%
13/24
|
|
Gastrointestinal disorders
Mucositis oral
|
33.3%
8/24
|
|
Musculoskeletal and connective tissue disorders
Muscle cramps
|
8.3%
2/24
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.2%
1/24
|
|
Cardiac disorders
Myocardial infarction
|
4.2%
1/24
|
|
Gastrointestinal disorders
Nausea
|
41.7%
10/24
|
|
General disorders
Neck edema
|
4.2%
1/24
|
|
Investigations
Neutrophil count decreased
|
37.5%
9/24
|
|
Cardiac disorders
Non-cardiac chest pain
|
12.5%
3/24
|
|
General disorders
Pain
|
12.5%
3/24
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.0%
6/24
|
|
Cardiac disorders
Pericardial effusion
|
4.2%
1/24
|
|
Gastrointestinal disorders
Periodontal disease
|
4.2%
1/24
|
|
Investigations
Platelet count decreased
|
50.0%
12/24
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.7%
4/24
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
20.8%
5/24
|
|
Renal and urinary disorders
Proteinuria
|
33.3%
8/24
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
6/24
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
16.7%
4/24
|
|
Skin and subcutaneous tissue disorders
Purpura
|
20.8%
5/24
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
66.7%
16/24
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Scalp pain
|
4.2%
1/24
|
|
Infections and infestations
Sepsis
|
4.2%
1/24
|
|
Cardiac disorders
Sinus bradycardia
|
12.5%
3/24
|
|
Cardiac disorders
Sinus tachycardia
|
8.3%
2/24
|
|
Infections and infestations
Sinusitis
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
4.2%
1/24
|
|
Infections and infestations
Skin infection
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
12.5%
3/24
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
12.5%
3/24
|
|
Infections and infestations
Splenic infarction
|
4.2%
1/24
|
|
Investigations
Splenomegaly
|
4.2%
1/24
|
|
Infections and infestations
Staphylococcus epidermidis
|
4.2%
1/24
|
|
Gastrointestinal disorders
Stomach pain
|
4.2%
1/24
|
|
Gastrointestinal disorders
Stomatitis
|
4.2%
1/24
|
|
Vascular disorders
Thromboembolic event - DVT
|
8.3%
2/24
|
|
Infections and infestations
Tooth infection
|
4.2%
1/24
|
|
Immune system disorders
Transfusion reaction
|
8.3%
2/24
|
|
Renal and urinary disorders
Urinary frequency
|
8.3%
2/24
|
|
Renal and urinary disorders
Urinary incontinence
|
4.2%
1/24
|
|
Infections and infestations
Urinary tract infection
|
4.2%
1/24
|
|
Renal and urinary disorders
Urinary tract pain
|
4.2%
1/24
|
|
Infections and infestations
VRE stool
|
16.7%
4/24
|
|
Ear and labyrinth disorders
Vertigo
|
4.2%
1/24
|
|
Gastrointestinal disorders
Vomiting
|
29.2%
7/24
|
|
Investigations
Weight loss
|
20.8%
5/24
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
12.5%
3/24
|
|
Investigations
White blood cell decreased
|
54.2%
13/24
|
Additional Information
Ravi Vij, M.D.
Washington University School of Medicine
Phone: 314-454-8304
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place