Back to resultsAdministration of Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tadalafil
Lenalidomide
Dexamethasone
Clarithromycin
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Progressive myeloma as defined by the International Uniform Criteria.
- Currently on Lenalidomide and dexamethasone for the treatment of myeloma
- Age > 18 years.
- Measurable paraprotein in serum or urine or detectable free light chains in the serum.
- ECOG performance status of 0 - 2.
Exclusion Criteria:
- Hypersensitivity to PDE5 inhibitors such as tadalafil, sildenafil or vardenafil.
- History of malignancy other than multiple myeloma in the last five years of, except adequately treated basal or squamous cell skin cancer.
- Participation in any clinical trial which involved an investigational drug or device four weeks prior.
- Infection requiring treatment with antibiotics, antifungal, or antiviral agents in the last seven days
- Any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
- History of significant hypotensive episode requiring hospitalization.
- Acute myocardial infarction within prior 3 months, uncontrolled angina
- Uncontrolled arrhythmia, or uncontrolled congestive heart failure
- History of any of the following cardiac conditions:
I. Angina requiring treatment with long-acting nitrates. II. Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration.
III. Unstable angina within 90 days of visit 1. IV. Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention.
- History of any of the following coronary conditions within 90 days of planned tadalafil administration:
i. Myocardial Infarction.
ii. Coronary artery bypass graft surgery.
iii. Percutaneous coronary intervention (for example, angioplasty or stent placement).
iv. Any evidence of heart disease (NYHA≥Class III) within 6 months of planned tadalafil administration.
- Current treatment with nitrates.
- Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitors such as ketoconazole or ritonavir.
- Prior chronic immune suppressive state (AIDS, immunosuppressive therapy).
- History of hypotension and/or blindness or sudden decrease/loss of hearing during prior treatment with PDE-5 inhibitors.
- Prior history of non-arterial ischemic optic retinopathy
Sites / Locations
- Sidney Kimmel Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tadalafil
Arm Description
Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd)
Outcomes
Primary Outcome Measures
Response Rate
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.
Secondary Outcome Measures
Duration of Response
Median length of response in months.
Time to Progression
Median time to progression of disease in days.
Quality of Life Scores
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.
Effect of PDE5 Inhibition on Immune Function as Assessed by MDSC Quantification
Percentage change in the amount of myeloid derived suppressor cells (MDSCs) in peripheral blood.
Full Information
NCT ID
NCT01374217
First Posted
June 13, 2011
Last Updated
November 9, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1. Study Identification
Unique Protocol Identification Number
NCT01374217
Brief Title
Administration of Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma
Official Title
Administration of an Oral PDE5 Inhibitor, Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Terminated
Why Stopped
early stopping rule
Study Start Date
April 2012 (Actual)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the anti-tumor efficacy of tadalafil in combination with Lenalidomide/dexamethasone (Rd) in multiple myeloma.
Detailed Description
This is an early phase study to evaluate the safety and efficacy of the combination of tadalafil with lenalidomide and dexamethasone (Rd) or BiRd. 19 patients on Rd or BiRd will be treated with tadalafil for a minimum of 6 months. The investigational drug will be discontinued if there is evidence of disease progression as defined by the International Uniform Response criteria [1]. For responding patients (patients who have a CR, VGPR, PR or SD), the therapy will be continued until progression or intolerable adverse effects. Blood and bone marrow will be collected for various studies as detailed in section 14.10. Clinical response will be monitored every month during the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tadalafil
Arm Type
Experimental
Arm Description
Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd)
Intervention Type
Drug
Intervention Name(s)
Tadalafil
Other Intervention Name(s)
Cialis
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide will be administered as it was prior to study entry.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
Dexamethasone will be administered as it was prior to study entry.
Intervention Type
Drug
Intervention Name(s)
Clarithromycin
Other Intervention Name(s)
Biaxin
Intervention Description
Clarithromycin will be administered as it was prior to study entry.
Primary Outcome Measure Information:
Title
Response Rate
Description
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.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Duration of Response
Description
Median length of response in months.
Time Frame
Up to 6 months
Title
Time to Progression
Description
Median time to progression of disease in days.
Time Frame
Up to 71 days
Title
Quality of Life Scores
Description
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.
Time Frame
3 months (M3) and 6 months (M6)
Title
Effect of PDE5 Inhibition on Immune Function as Assessed by MDSC Quantification
Description
Percentage change in the amount of myeloid derived suppressor cells (MDSCs) in peripheral blood.
Time Frame
Up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Progressive myeloma as defined by the International Uniform Criteria.
Currently on Lenalidomide and dexamethasone for the treatment of myeloma
Age > 18 years.
Measurable paraprotein in serum or urine or detectable free light chains in the serum.
ECOG performance status of 0 - 2.
Exclusion Criteria:
Hypersensitivity to PDE5 inhibitors such as tadalafil, sildenafil or vardenafil.
History of malignancy other than multiple myeloma in the last five years of, except adequately treated basal or squamous cell skin cancer.
Participation in any clinical trial which involved an investigational drug or device four weeks prior.
Infection requiring treatment with antibiotics, antifungal, or antiviral agents in the last seven days
Any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
History of significant hypotensive episode requiring hospitalization.
Acute myocardial infarction within prior 3 months, uncontrolled angina
Uncontrolled arrhythmia, or uncontrolled congestive heart failure
History of any of the following cardiac conditions:
I. Angina requiring treatment with long-acting nitrates. II. Angina requiring treatment with short-acting nitrates within 90 days of planned tadalafil administration.
III. Unstable angina within 90 days of visit 1. IV. Positive cardiac stress test without documented evidence of subsequent, effective cardiac intervention.
- History of any of the following coronary conditions within 90 days of planned tadalafil administration:
i. Myocardial Infarction.
ii. Coronary artery bypass graft surgery.
iii. Percutaneous coronary intervention (for example, angioplasty or stent placement).
iv. Any evidence of heart disease (NYHA≥Class III) within 6 months of planned tadalafil administration.
Current treatment with nitrates.
Current systemic treatment with a potent cytochrome P450 3A4 (CYP3A4) inhibitors such as ketoconazole or ritonavir.
Prior chronic immune suppressive state (AIDS, immunosuppressive therapy).
History of hypotension and/or blindness or sudden decrease/loss of hearing during prior treatment with PDE-5 inhibitors.
Prior history of non-arterial ischemic optic retinopathy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nilanjan Ghosh, M.D., Ph.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Administration of Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma
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