Trial Outcomes & Findings for Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma (NCT NCT00967044)
NCT ID: NCT00967044
Last Updated: 2015-02-26
Results Overview
MTD of the novel combination of Everolimus + Panobinostat (LBH589) in a phase-I study in participants with relapsed lymphoma (Hodgkin and non-Hodgkin) where MTD is defined as the highest dose at which no more than 1 in 6 of the participants in the cohort experiences one or more dose limiting toxicities (DLTs) in the first 28 day treatment cycle. Thirty patients were enrolled onto four dose levels: Everolimus (mg, orally) 5, 5, 10, 10 daily or Panobinostat (mg, orally) 10, 20, 20, 30 three times per week. The MTD was established without the use of colony stimulating factor in cycle 1.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
31 participants
Primary outcome timeframe
28 day treatment cycle
Results posted on
2015-02-26
Participant Flow
Recruitment Period: November 25, 2009 to February 17, 2012. All recruitment was done at University of Texas (UT) MD Anderson Cancer Center.
Of the 31 participants recruited, one participant was excluded from the study as a screen failure.
Participant milestones
| Measure |
Panobinostat + Everolimus
Panobinostat (LBH589) Plus Everolimus (RAD001)
Panobinostat: Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week
Everolimus: Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
Baseline characteristics by cohort
| Measure |
Panobinostat + Everolimus
n=30 Participants
Panobinostat (LBH589) Plus Everolimus (RAD001)
Panobinostat: Starting dose of 10 mg by mouth per day, self-administered (by participants), three times per week.
Everolimus: Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
|
|---|---|
|
Age, Continuous
|
52 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=99 Participants
|
|
Participation by Cohort
Panobinostat 10 mg/Everolimus 5 mg
|
3 participants
n=99 Participants
|
|
Participation by Cohort
Panobinostat 20 mg/Everolimus 5 mg
|
3 participants
n=99 Participants
|
|
Participation by Cohort
Panobinostat 20 mg/Everolimus 10 mg
|
22 participants
n=99 Participants
|
|
Participation by Cohort
Panobinostat 30 mg/Everolimus 10 mg
|
2 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 28 day treatment cycleMTD of the novel combination of Everolimus + Panobinostat (LBH589) in a phase-I study in participants with relapsed lymphoma (Hodgkin and non-Hodgkin) where MTD is defined as the highest dose at which no more than 1 in 6 of the participants in the cohort experiences one or more dose limiting toxicities (DLTs) in the first 28 day treatment cycle. Thirty patients were enrolled onto four dose levels: Everolimus (mg, orally) 5, 5, 10, 10 daily or Panobinostat (mg, orally) 10, 20, 20, 30 three times per week. The MTD was established without the use of colony stimulating factor in cycle 1.
Outcome measures
| Measure |
Panobinostat + Everolimus
n=30 Participants
Panobinostat (LBH589) Plus Everolimus (RAD001)
Panobinostat: Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week
Everolimus: Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat
Everolimus (daily)
|
10 mg, orally
|
|
Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat
Panobinostat (three times weekly)
|
20 mg, orally
|
Adverse Events
Panobinostat + Everolimus
Serious events: 19 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Panobinostat + Everolimus
n=30 participants at risk
Panobinostat (LBH589) Plus Everolimus (RAD001)
Panobinostat: Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week
Everolimus: Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
|
|---|---|
|
General disorders
Fatigue
|
6.7%
2/30 • Number of events 2 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.7%
2/30 • Number of events 2 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Gastrointestinal disorders
Diarrhea
|
3.3%
1/30 • Number of events 1 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.3%
1/30 • Number of events 1 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
3.3%
1/30 • Number of events 1 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Infections and infestations
Febrile neutropenia
|
6.7%
2/30 • Number of events 2 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Infections and infestations
Other Infection
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
6/30 • Number of events 6 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Neutropenia
|
46.7%
14/30 • Number of events 14 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Hemorrhage
|
3.3%
1/30 • Number of events 1 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
63.3%
19/30 • Number of events 19 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
Other adverse events
| Measure |
Panobinostat + Everolimus
n=30 participants at risk
Panobinostat (LBH589) Plus Everolimus (RAD001)
Panobinostat: Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week
Everolimus: Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
|
|---|---|
|
General disorders
Anorexia
|
56.7%
17/30 • Number of events 17 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Weight loss
|
33.3%
10/30 • Number of events 10 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Fatigue
|
83.3%
25/30 • Number of events 25 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Dizziness
|
20.0%
6/30 • Number of events 6 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Edema
|
26.7%
8/30 • Number of events 8 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Nausea
|
33.3%
10/30 • Number of events 10 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Vomit
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Pain
|
40.0%
12/30 • Number of events 12 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
General disorders
Rigors
|
16.7%
5/30 • Number of events 5 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Cardiac disorders
Hypotension
|
20.0%
6/30 • Number of events 6 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Cardiac disorders
QTc prolongation
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
43.3%
13/30 • Number of events 13 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
43.3%
13/30 • Number of events 13 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Gastrointestinal disorders
Elevated ALKP
|
16.7%
5/30 • Number of events 5 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Gastrointestinal disorders
Elevated AST
|
26.7%
8/30 • Number of events 8 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Gastrointestinal disorders
Diarrhea
|
46.7%
14/30 • Number of events 14 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Gastrointestinal disorders
Mucositis
|
60.0%
18/30 • Number of events 18 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
63.3%
19/30 • Number of events 19 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
13.3%
4/30 • Number of events 4 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
13.3%
4/30 • Number of events 4 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypomagnesiemia
|
16.7%
5/30 • Number of events 5 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
33.3%
10/30 • Number of events 10 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Nervous system disorders
Dysphasia
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Nervous system disorders
Sensory neuropathy
|
26.7%
8/30 • Number of events 8 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Nervous system disorders
Taste change
|
23.3%
7/30 • Number of events 7 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Renal and urinary disorders
Elevated creatinine
|
20.0%
6/30 • Number of events 6 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Skin and subcutaneous tissue disorders
Acne
|
13.3%
4/30 • Number of events 4 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
5/30 • Number of events 5 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
13.3%
4/30 • Number of events 4 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
10/30 • Number of events 10 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Ear and labyrinth disorders
Rhinitis
|
23.3%
7/30 • Number of events 7 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Infections and infestations
Non-neutropenic fever
|
33.3%
10/30 • Number of events 10 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Infections and infestations
Other infection
|
20.0%
6/30 • Number of events 6 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Anemia
|
53.3%
16/30 • Number of events 16 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
2/30 • Number of events 2 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Hemorrhage
|
13.3%
4/30 • Number of events 4 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
3/30 • Number of events 3 • Adverse event reporting with each 28 day treatment cycle. Overall study participation from December 2009 to April 2012.
|
Additional Information
Yasuhiro Oki, MD / Assistant Professor, Lymphoma/Myeloma
University of Texas MD Anderson Cancer Center
Phone: 713-792-2860
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place