Clinical trial NCT01374217: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2011-06-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response Rate
timeFrame: Up to 6 months
Secondary outcomes:
measure: Duration of Response
timeFrame: Up to 6 months
measure: Time to Progression
timeFrame: Up to 71 days
measure: Quality of Life Scores
timeFrame: 3 months (M3) and 6 months (M6)
measure: Effect of PDE5 Inhibition on Immune Function as Assessed by MDSC Quantification
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Nilanjan Ghosh, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: