Administration of Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Tadalafil; Lenalidomide; Dexamethasone; Clarithromycin
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; Lenalidomide will be administered as it was prior to study entry.; Dexamethasone will be administered as it was prior to study entry.; Clarithromycin will be administered as it was prior to study entry.
Intervention MeSH terms: Clarithromycin; Dexamethasone; Lenalidomide; Tadalafil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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