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

NCT ID: NCT01374217

Last Updated: 2018-12-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-01-31

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tadalafil

Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd)

Group Type: EXPERIMENTAL

Tadalafil

Intervention Type: DRUG

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

Intervention Type: DRUG

Lenalidomide will be administered as it was prior to study entry.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered as it was prior to study entry.

Clarithromycin

Intervention Type: DRUG

Clarithromycin will be administered as it was prior to study entry.

Interventions

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

Intervention Type: DRUG

Lenalidomide

Lenalidomide will be administered as it was prior to study entry.

Intervention Type: DRUG

Dexamethasone

Dexamethasone will be administered as it was prior to study entry.

Intervention Type: DRUG

Clarithromycin

Clarithromycin will be administered as it was prior to study entry.

Intervention Type: DRUG

Other Intervention Names

Cialis; Revlimid; Decadron; Biaxin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nilanjan Ghosh, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NA_00049238

Identifier Type: OTHER

Identifier Source: secondary_id

J1167

Identifier Type: -

Identifier Source: org_study_id