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

This study has been terminated.
(early stopping rule)
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01374217
First received: June 13, 2011
Last updated: March 23, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: Tadalafil, Cialis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Anti-tumor efficacy of tadalafil, Lenalidomide/dexamethasone in multiple myeloma [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    Hypothesis testing will be used to test the null that 5% patients will have a response versus the alternative hypothesis of 25% (a 20% improvement). If 3 or more out of 19 patients had response, the null hypothesis is rejected at a type I error rate of 0.05 (one-sided) given 20% type II error rate.

    If initial review after 12 patients shows at least 1 response, 7 more patients will be enrolled. The therapy will be continued until progression or intolerable adverse effects. Clinical response will be evaluated by calculating the increase or decrease in the M-protein levels in blood and marrow.



Secondary Outcome Measures:
  • Safety [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Review of the type, frequency, severity, and relationship of adverse events to the study drug


Enrollment: 14
Study Start Date: August 2011
Estimated Study Completion Date: February 2015
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tadalafil (Cialis)
Subject will take tadalafil(cialis) in combination with with Lenalidomide and dexamethasone (Rd) or Biaxin/Lenalidomide/ dexamethasone (BiRd)
Drug: Tadalafil, Cialis
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01374217

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore,, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Nilanjan Ghosh, M.D., Ph.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01374217     History of Changes
Other Study ID Numbers: J1167, NA_00049238
Study First Received: June 13, 2011
Last Updated: March 23, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
BB 1101
Tadalafil
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 18, 2014