Trial Outcomes & Findings for Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS (NCT NCT01442714)
NCT ID: NCT01442714
Last Updated: 2018-01-03
Results Overview
Overall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR).
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
203 days
Results posted on
2018-01-03
Participant Flow
Participant milestones
| Measure |
Azacitidine Plus Lenalidomide
Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.
Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death
Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory
|
|---|---|
|
Overall Study
STARTED
|
33
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
Azacitidine Plus Lenalidomide
Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.
Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death
Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory
|
|---|---|
|
Overall Study
Death
|
11
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS
Baseline characteristics by cohort
| Measure |
Azacitidine Plus Lenalidomide
n=33 Participants
Azacitidine + Lenalidomide Combo
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 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
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
0
|
24 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
1
|
6 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
2
|
3 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Not eligible
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 203 daysOverall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR).
Outcome measures
| Measure |
Azacitidine Plus Lenalidomide
n=33 Participants
Acute myeloid leukemia (AML) ORR was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR): (CR + CRi + PR)
|
|---|---|
|
Overall Response Rate (ORR)
|
5 Participants
|
SECONDARY outcome
Timeframe: 203 daysThe median duration of response was defined by the median duration of response for participants with Complete Response (CR); CR with incomplete count recovery (CRi); or Partial Response (PR).
Outcome measures
| Measure |
Azacitidine Plus Lenalidomide
n=5 Participants
Acute myeloid leukemia (AML) ORR was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR): (CR + CRi + PR)
|
|---|---|
|
Median Duration of Response
|
118 days
Interval 56.48 to 349.5
|
SECONDARY outcome
Timeframe: 462 DaysSurvival was measured from the 1st day of azacitidine treatment to death from any cause.
Outcome measures
| Measure |
Azacitidine Plus Lenalidomide
n=33 Participants
Acute myeloid leukemia (AML) ORR was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR): (CR + CRi + PR)
|
|---|---|
|
Overall Survival
|
5 months
Interval 3.7 to 8.6
|
Adverse Events
Azacitidine Plus Lenalidomide
Serious events: 33 serious events
Other events: 33 other events
Deaths: 30 deaths
Serious adverse events
| Measure |
Azacitidine Plus Lenalidomide
n=33 participants at risk
Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.
Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death
Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory.
|
|---|---|
|
Infections and infestations
Neutropenic fever
|
75.8%
25/33 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory complications
|
24.2%
8/33 • 16 months
|
|
Gastrointestinal disorders
Diarrhea
|
3.0%
1/33 • 16 months
|
|
Gastrointestinal disorders
Gastrointestinal Bleeding
|
3.0%
1/33 • 16 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.0%
1/33 • 16 months
|
|
Infections and infestations
Sepsis
|
6.1%
2/33 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Death on study
|
33.3%
11/33 • 16 months
|
|
Cardiac disorders
Cardiac complications
|
6.1%
2/33 • 16 months
|
|
Blood and lymphatic system disorders
Pancytopenia
|
6.1%
2/33 • 16 months
|
|
Gastrointestinal disorders
Colon Volvulus
|
3.0%
1/33 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain and stiffness
|
3.0%
1/33 • 16 months
|
|
Infections and infestations
Progressive disease
|
6.1%
2/33 • 16 months
|
|
General disorders
Cellulitis
|
6.1%
2/33 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Generalized weakness
|
6.1%
2/33 • 16 months
|
|
General disorders
Graft vs host disease (GvHD)
|
3.0%
1/33 • 16 months
|
|
Infections and infestations
Neck complications
|
6.1%
2/33 • 16 months
|
|
General disorders
Rigors secondary to fever
|
3.0%
1/33 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Body pain
|
6.1%
2/33 • 16 months
|
|
Nervous system disorders
Encephalopathy
|
3.0%
1/33 • 16 months
|
|
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation
|
3.0%
1/33 • 16 months
|
|
Gastrointestinal disorders
Vomitting
|
3.0%
1/33 • 16 months
|
|
Skin and subcutaneous tissue disorders
Skin infections
|
6.1%
2/33 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Hypoxia
|
3.0%
1/33 • 16 months
|
|
General disorders
Fever
|
6.1%
2/33 • 16 months
|
Other adverse events
| Measure |
Azacitidine Plus Lenalidomide
n=33 participants at risk
Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.
Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death
Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory.
|
|---|---|
|
Nervous system disorders
Neuropathy
|
6.1%
2/33 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Edema
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
apneic
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Musculoskeletal and connective tissue disorders
back pain
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Crackles at right base of lung
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Cramps
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Gastrointestinal disorders
Decreased appetite
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Dehydration
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Renal and urinary disorders
Difficulty urinating
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
9.1%
3/33 • Number of events 3 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Fungal pneumonia
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Cardiac disorders
Left carotid
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Skin and subcutaneous tissue disorders
skin nodules
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Cardiac disorders
Tachycardiac
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Skin and subcutaneous tissue disorders
Ecchymoses on site injections
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Renal and urinary disorders
Elevated LFT (AST>AST)
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Blood and lymphatic system disorders
Epistaxis
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Infections and infestations
erythema and conjunctival injection of right eye
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Infections and infestations
erythematous lesions at injection site at abdomen
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Fall
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Fever
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
fracture of left fibula
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Frontal headache
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Hoarse voice
|
9.1%
3/33 • Number of events 3 • 16 months
|
|
Blood and lymphatic system disorders
hyperglycemic
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Blood and lymphatic system disorders
Hypotensive
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Blood and lymphatic system disorders
Hypertrophy of her gums
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Gastrointestinal disorders
epigastic pain after eating
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Cardiac disorders
episodes of chest pressure
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Skin and subcutaneous tissue disorders
Large bruise
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Left hip injury
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Left leg pain
|
9.1%
3/33 • Number of events 3 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
left thyroid nodule
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Mild erythema at abdominal injection site
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Mouth soures/ thrush
|
12.1%
4/33 • Number of events 4 • 16 months
|
|
General disorders
Night sweat
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Nose bleeds
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Open sore of lower lip
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Eye disorders
Redness and itching of eyes
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Musculoskeletal and connective tissue disorders
Tremors
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
Blood and lymphatic system disorders
Significant Cytopenias
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
sore tongue
|
6.1%
2/33 • Number of events 2 • 16 months
|
|
General disorders
stress incontinence
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Eye disorders
Sudden loss of central vision
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
Swollen Knee
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Taste changes
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
tender facial skin
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Cardiac disorders
Unspecified arrhythmia
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
General disorders
weight loss
|
3.0%
1/33 • Number of events 1 • 16 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergies
|
3.0%
1/33 • Number of events 1 • 16 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place