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

Multiple Myeloma Clinical Trial

Official title:

Administration of an Oral PDE5 Inhibitor, Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01374217
• Other study ID #: J1167
• Secondary ID: NA_00049238
• Status: Terminated
• Phase: Phase 2
• Start date: April 2012
• Est. completion date: January 2014

Study information

• Verified date: November 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 6 months
Secondary	Duration of Response	Median length of response in months.	Up to 6 months
Secondary	Time to Progression	Median time to progression of disease in days.	Up to 71 days
Secondary	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.	3 months (M3) and 6 months (M6)
Secondary	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.	Up to 6 months