Trial Outcomes & Findings for LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis (NCT NCT02098161)
NCT ID: NCT02098161
Last Updated: 2023-06-06
Results Overview
Will be defined as complete remission (CR), partial remission (PR), or clinical improvement (CI) after 3 courses of treatment according to International Working Group (IWG) consensus criteria for myelofibrosis. Complete remission (CR): bone marrow blasts \<5%, hemoglobin \>/= 10, absolute neutrophil count (ANC) \>/= 1000, platelets \>/= 100, \<2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC \>/= 1000, decreased platelets by 50%, hemoglobin \>/= 8.5 but \< 10, \<2% immature myeloid cells. Clinical improvement (CI): hemoglobin increase of 2g/dl, transfusion independence or reduction splenomegaly and/or hepatomegaly \>/= 50%, \>/=50% reduction in MPN-SAF TSS
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
After 3 courses of Therapy
Results posted on
2023-06-06
Participant Flow
Participant milestones
| Measure |
Treatment (SMAC Mimetic LCL161)
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Overall Study
STARTED
|
50
|
|
Overall Study
COMPLETED
|
50
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis
Baseline characteristics by cohort
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 Participants
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
37 Participants
n=5 Participants
|
|
Age, Continuous
|
72 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 3 courses of TherapyWill be defined as complete remission (CR), partial remission (PR), or clinical improvement (CI) after 3 courses of treatment according to International Working Group (IWG) consensus criteria for myelofibrosis. Complete remission (CR): bone marrow blasts \<5%, hemoglobin \>/= 10, absolute neutrophil count (ANC) \>/= 1000, platelets \>/= 100, \<2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC \>/= 1000, decreased platelets by 50%, hemoglobin \>/= 8.5 but \< 10, \<2% immature myeloid cells. Clinical improvement (CI): hemoglobin increase of 2g/dl, transfusion independence or reduction splenomegaly and/or hepatomegaly \>/= 50%, \>/=50% reduction in MPN-SAF TSS
Outcome measures
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 Participants
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Number of Participants With a Response
|
15 Participants
|
SECONDARY outcome
Timeframe: Up to 7 years 5 Monthsduration of response is defined as the date at which the subject's objective status is first noted to be a CR or PR to the date progression is documented (if one has occurred) or to the date of last follow-up (for those subjects who have not progressed).
Outcome measures
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 Participants
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Duration of Response
|
31.5 Months
Interval 3.6 to 59.2
|
SECONDARY outcome
Timeframe: Up to 7 years 5 monthsThe time to response is defined as the time from study registration to the first date at which the subject's objective status was classified as a response (CR or PR). In subjects who do not achieve a response, time to response will be censored at the subject's last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) will be estimated by Kaplan-Meier curves.
Outcome measures
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 Participants
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Time to Response
|
1.4 Months
Interval 0.9 to 9.1
|
SECONDARY outcome
Timeframe: Up to 7 years 5 monthsTime from date of treatment start until date of death due to any cause or last Follow-up.
Outcome measures
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 Participants
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Overall Survival
|
34 Months
Interval 2.2 to 60.1
|
Adverse Events
Treatment (SMAC Mimetic LCL161)
Serious events: 33 serious events
Other events: 50 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 participants at risk
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
4.0%
2/50 • Number of events 3 • Up to 7 years 5 months
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Immune system disorders
Allergic reaction
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Blood and lymphatic system disorders
Anemia
|
10.0%
5/50 • Number of events 5 • Up to 7 years 5 months
|
|
Psychiatric disorders
Anxiety
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Cardiac disorders
Atrial fibrillation
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Cardiac disorders
Chest pain cardiac
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Colitis
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Psychiatric disorders
Confusion
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Diarrhea
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Injury, poisoning and procedural complications
Fall
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
General disorders
Fatigue
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
General disorders
Fever
|
10.0%
5/50 • Number of events 5 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Infections and infestations
Infections and infestations
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Nervous system disorders
Intracranial hemorrhage
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Infections and infestations
Lung infection
|
18.0%
9/50 • Number of events 11 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Nausea
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
6.0%
3/50 • Number of events 6 • Up to 7 years 5 months
|
|
Nervous system disorders
Nervous system disorders
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
General disorders
Pain
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Investigations
Platelet count decreased
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
2.0%
1/50 • Number of events 2 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
2.0%
1/50 • Number of events 6 • Up to 7 years 5 months
|
|
Infections and infestations
Sepsis
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Nervous system disorders
Stroke
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
|
Surgical and medical procedures
Surgical and medical procedures
|
4.0%
2/50 • Number of events 2 • Up to 7 years 5 months
|
|
Nervous system disorders
Syncope
|
6.0%
3/50 • Number of events 4 • Up to 7 years 5 months
|
|
Infections and infestations
Urinary tract infection
|
2.0%
1/50 • Number of events 1 • Up to 7 years 5 months
|
Other adverse events
| Measure |
Treatment (SMAC Mimetic LCL161)
n=50 participants at risk
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
Smac Mimetic LCL161: Given PO
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Psychiatric disorders
Anxiety
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Ascites
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Psychiatric disorders
Confusion
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Metabolism and nutrition disorders
Dehydration
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Dry mouth
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Vascular disorders
Flushing
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
General disorders
Gait disturbance
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Nervous system disorders
Lightheadedness
|
8.0%
4/50 • Number of events 4 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Ear and labyrinth disorders
Tinnitus
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Ear and labyrinth disorders
Vertigo
|
6.0%
3/50 • Number of events 3 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
6.0%
3/50 • Number of events 4 • Up to 7 years 5 months
|
|
Nervous system disorders
Memory impairment
|
8.0%
4/50 • Number of events 4 • Up to 7 years 5 months
|
|
Infections and infestations
Urinary tract infection
|
8.0%
4/50 • Number of events 4 • Up to 7 years 5 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.0%
5/50 • Number of events 5 • Up to 7 years 5 months
|
|
General disorders
Malaise
|
8.0%
4/50 • Number of events 5 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
5/50 • Number of events 5 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
10.0%
5/50 • Number of events 5 • Up to 7 years 5 months
|
|
General disorders
Flu like symptoms
|
12.0%
6/50 • Number of events 6 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
10.0%
5/50 • Number of events 6 • Up to 7 years 5 months
|
|
Renal and urinary disorders
Urinary frequency
|
12.0%
6/50 • Number of events 6 • Up to 7 years 5 months
|
|
Metabolism and nutrition disorders
Anorexia
|
14.0%
7/50 • Number of events 7 • Up to 7 years 5 months
|
|
Injury, poisoning and procedural complications
Bruising
|
16.0%
8/50 • Number of events 8 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.0%
8/50 • Number of events 8 • Up to 7 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.0%
8/50 • Number of events 8 • Up to 7 years 5 months
|
|
General disorders
Chills
|
18.0%
9/50 • Number of events 9 • Up to 7 years 5 months
|
|
Injury, poisoning and procedural complications
Fall
|
16.0%
8/50 • Number of events 9 • Up to 7 years 5 months
|
|
Vascular disorders
Hypotension
|
18.0%
9/50 • Number of events 9 • Up to 7 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.0%
8/50 • Number of events 9 • Up to 7 years 5 months
|
|
General disorders
night sweats
|
14.0%
7/50 • Number of events 9 • Up to 7 years 5 months
|
|
Psychiatric disorders
Insomnia
|
16.0%
8/50 • Number of events 10 • Up to 7 years 5 months
|
|
Investigations
Weight loss
|
20.0%
10/50 • Number of events 10 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Constipation
|
24.0%
12/50 • Number of events 12 • Up to 7 years 5 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
22.0%
11/50 • Number of events 13 • Up to 7 years 5 months
|
|
Surgical and medical procedures
Surgical and medical procedures
|
12.0%
6/50 • Number of events 13 • Up to 7 years 5 months
|
|
General disorders
Fever
|
28.0%
14/50 • Number of events 14 • Up to 7 years 5 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
28.0%
14/50 • Number of events 14 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Abdominal distension
|
30.0%
15/50 • Number of events 15 • Up to 7 years 5 months
|
|
General disorders
Headache
|
30.0%
15/50 • Number of events 15 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
40.0%
20/50 • Number of events 22 • Up to 7 years 5 months
|
|
General disorders
Edema limbs
|
38.0%
19/50 • Number of events 20 • Up to 7 years 5 months
|
|
Investigations
Investigations
|
16.0%
8/50 • Number of events 20 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
20/50 • Number of events 20 • Up to 7 years 5 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo papular
|
42.0%
21/50 • Number of events 21 • Up to 7 years 5 months
|
|
Nervous system disorders
Dizziness
|
46.0%
23/50 • Number of events 23 • Up to 7 years 5 months
|
|
Infections and infestations
Infection
|
30.0%
15/50 • Number of events 23 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Diarrhea
|
54.0%
27/50 • Number of events 27 • Up to 7 years 5 months
|
|
General disorders
Pain
|
66.0%
33/50 • Number of events 60 • Up to 7 years 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
56.0%
28/50 • Number of events 28 • Up to 7 years 5 months
|
|
Gastrointestinal disorders
Nausea
|
70.0%
35/50 • Number of events 35 • Up to 7 years 5 months
|
|
General disorders
Fatigue
|
74.0%
37/50 • Number of events 37 • Up to 7 years 5 months
|
Additional Information
Naveen Pemmaraju MD/ Associate Professor
The University of Texas MD Anderson Cancer Center
Phone: 713-792-4956
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place