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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01374217
Recruitment Status : Terminated (early stopping rule)
First Posted : June 15, 2011
Results First Posted : December 10, 2018
Last Update Posted : December 10, 2018
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Tadalafil Drug: Lenalidomide Drug: Dexamethasone Drug: Clarithromycin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Administration of an Oral PDE5 Inhibitor, Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma
Actual Study Start Date : April 2012
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Arm Intervention/treatment
Experimental: Tadalafil
Subject will take tadalafil in combination with with Lenalidomide and dexamethasone (Rd) or Clarithromycin/Lenalidomide/ dexamethasone (BiRd)
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
Other Name: Cialis

Drug: Lenalidomide
Lenalidomide will be administered as it was prior to study entry.
Other Name: Revlimid

Drug: Dexamethasone
Dexamethasone will be administered as it was prior to study entry.
Other Name: Decadron

Drug: Clarithromycin
Clarithromycin will be administered as it was prior to study entry.
Other Name: Biaxin

Primary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 6 months ]
    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 :
  1. Duration of Response [ Time Frame: Up to 6 months ]
    Median length of response in months.

  2. Time to Progression [ Time Frame: Up to 71 days ]
    Median time to progression of disease in days.

  3. Quality of Life Scores [ Time Frame: 3 months (M3) and 6 months (M6) ]
    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.

  4. Effect of PDE5 Inhibition on Immune Function as Assessed by MDSC Quantification [ Time Frame: Up to 6 months ]
    Percentage change in the amount of myeloid derived suppressor cells (MDSCs) in peripheral blood.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01374217

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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Principal Investigator: Nilanjan Ghosh, M.D., Ph.D. Johns Hopkins University
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT01374217    
Other Study ID Numbers: J1167
NA_00049238 ( Other Identifier: JHMI IRB )
First Posted: June 15, 2011    Key Record Dates
Results First Posted: December 10, 2018
Last Update Posted: December 10, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors