Trial Outcomes & Findings for Administration of Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma (NCT NCT01374217)

Last Updated: 2018-12-10

Results Overview

Percentage of participants who responded to the addition of tadalafil. Response is defined as a complete remission (CR), very good partial remission (VGPR), partial remission (PR), or stable disease (SD) by International Uniform Response criteria.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2018-12-10

Participant Flow

One participant was a screen failure.

Participant milestones

Participant milestones
Measure	Tadalafil Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Overall Study STARTED	13
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Tadalafil Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Overall Study Lack of Efficacy	13

Baseline Characteristics

Administration of Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tadalafil n=13 Participants Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: One participant was not analyzed because he only received eight days of study drug prior to progression and removal from study. One participant was retrospectively ineligible and was therefore not analyzed.

Outcome measures

Outcome measures
Measure	Tadalafil n=11 Participants Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Response Rate	5 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: This analysis only includes the 5 participants who had a clinical response.

Median length of response in months.

Outcome measures

Outcome measures
Measure	Tadalafil n=5 Participants Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Duration of Response	2.3 months Interval 1.6 to 5.3

SECONDARY outcome

Timeframe: Up to 71 days

Median time to progression of disease in days.

Outcome measures

Outcome measures
Measure	Tadalafil n=11 Participants Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Time to Progression	48 days Interval 25.0 to 71.0

SECONDARY outcome

Timeframe: 3 months (M3) and 6 months (M6)

Population: Two participants returned the Month 3 survey and seven participants returned the Month 6 survey (there is some overlap). The remaining participants cannot be analyzed as there is no follow-up data.

Median change in symptom scores. Scale is the EORTC QLQ-C30. There are three domains: symptom scale (score range 7-14); past week (score range 21-82); and global health status (score range 2-14). Higher or increasing scores mean worse outcomes; lower or decreasing scores mean better outcomes.

Outcome measures

Outcome measures
Measure	Tadalafil n=8 Participants Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Quality of Life Scores Symptoms (M3)	0 change in score on a scale Interval 0.0 to 0.0
Quality of Life Scores Past week (M3)	5 change in score on a scale Interval -1.0 to 11.0
Quality of Life Scores Global health status (M3)	-1.5 change in score on a scale Interval -3.0 to 0.0
Quality of Life Scores Symptoms (M6)	1 change in score on a scale Interval -1.0 to 3.0
Quality of Life Scores Past week (M6)	6 change in score on a scale Interval -4.0 to 9.0
Quality of Life Scores Global health status (M6)	-1 change in score on a scale Interval -7.0 to 0.0

SECONDARY outcome

Timeframe: Up to 6 months

Population: Data was not collected to assess this outcome measure.

Percentage change in the amount of myeloid derived suppressor cells (MDSCs) in peripheral blood.

Outcome measures

Outcome data not reported

Adverse Events

Tadalafil

Serious events: 0 serious events

Other events: 13 other events

Deaths: 6 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tadalafil n=13 participants at risk Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd) Tadalafil: Tadalafil will be administered at a dose of 20 mg orally daily starting with day 1 of the first cycle. Each cycle will last for 28 days Lenalidomide: Lenalidomide will be administered as it was prior to study entry. Dexamethasone: Dexamethasone will be administered as it was prior to study entry. Clarithromycin: Clarithromycin will be administered as it was prior to study entry.
Gastrointestinal disorders Anorexia	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Blurred vision	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
General disorders Cold intolerance	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Constipation	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Diarrhea	38.5% 5/13 • Number of events 6 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Dizziness	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Dyspepsia	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Respiratory, thoracic and mediastinal disorders Dyspnea	15.4% 2/13 • Number of events 3 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Eye floaters	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
General disorders Fatigue	69.2% 9/13 • Number of events 11 • Up to 7 months Adverse events were collected monthly.
Infections and infestations Fever	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Flatulence	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders GI bleed	23.1% 3/13 • Number of events 3 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Headache	30.8% 4/13 • Number of events 4 • Up to 7 months Adverse events were collected monthly.
Investigations High creatinine	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Investigations Hyperglycemia	61.5% 8/13 • Number of events 14 • Up to 7 months Adverse events were collected monthly.
Investigations Hypoalbuminemia	15.4% 2/13 • Number of events 3 • Up to 7 months Adverse events were collected monthly.
Investigations Hypocalcemia	30.8% 4/13 • Number of events 9 • Up to 7 months Adverse events were collected monthly.
Investigations Hypokalemia	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Insomnia	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Investigations Lymphopenia	53.8% 7/13 • Number of events 22 • Up to 7 months Adverse events were collected monthly.
Investigations Neutropenia	76.9% 10/13 • Number of events 22 • Up to 7 months Adverse events were collected monthly.
Investigations Low carbon dioxide	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Investigations Anemia	100.0% 13/13 • Number of events 33 • Up to 7 months Adverse events were collected monthly.
Investigations Thrombocytopenia	69.2% 9/13 • Number of events 23 • Up to 7 months Adverse events were collected monthly.
Investigations Leukopenia	84.6% 11/13 • Number of events 25 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Impaired memory	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Mucositis	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Nausea	30.8% 4/13 • Number of events 4 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Neuropathy	46.2% 6/13 • Number of events 9 • Up to 7 months Adverse events were collected monthly.
Infections and infestations Neutropenic fever	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
General disorders Night sweats	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
General disorders Epistaxis	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Osteonecrosis of the jaw	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Pain - back	53.8% 7/13 • Number of events 12 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Pain - bone	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Pain - hip	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Pain - rib	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Musculoskeletal and connective tissue disorders Pain - shoulder	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Skin and subcutaneous tissue disorders Pain - throat	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Eye disorders Red eyes	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Infections and infestations Upper respiratory infection	15.4% 2/13 • Number of events 2 • Up to 7 months Adverse events were collected monthly.
Nervous system disorders Hallucinations	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
General disorders Weight gain	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
General disorders Weight loss	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Respiratory, thoracic and mediastinal disorders Wheezing	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.
Skin and subcutaneous tissue disorders Xerosis	7.7% 1/13 • Number of events 1 • Up to 7 months Adverse events were collected monthly.

Additional Information

Nilanjan Ghosh, MD

Carolinas HealthCare System

Phone: 9804422000

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place