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Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma (RVDD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00724568
First received: April 11, 2008
Last updated: June 14, 2016
Last verified: June 2016
  Purpose
This research study is evaluating an investigational combination of four drugs called Revlimid® (lenalidomide), Velcade® (bortezomib), Dexamethasone and Doxil® (RVDD) as a possible treatment for newly diagnosed multiple myeloma.

Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: Bortezomib
Drug: Dexamethasone
Drug: Doxil
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Institutional Phase I/II Study of Revlimid® (Lenalidomide), Velcade® (Bortezomib), Dexamethasone, and Doxil®, (RVDD) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) [ Time Frame: 1 month post treatment ] [ Designated as safety issue: Yes ]

    Dose Level 1:

    15 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4

    Dose Level 2:

    20 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4

    Dose Level 3:

    25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4

    Dose Level 4:

    25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 30 mg/m2 Doxil daily on day 4



Secondary Outcome Measures:
  • The Percentage of Patients That Achieved Partial or Complete Response to Treatment. [ Time Frame: 24 weeks (8, 21-day cycles) ] [ Designated as safety issue: Yes ]

    Partial Response:

    • 50% reduction in the level of serum monoclonal protein for at least two determinations six weeks apart.
    • If present, reduction in 24-hour urinary light chain excretion by either, greater than or equal to 90%, or to <200 mg for at least two determinations six weeks apart.
    • 50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least six weeks.
    • No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).

    Complete Response:

    • Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of six weeks.
    • <5% plasma cells in the bone marrow on at least two determinations for a minimum of six weeks.
    • No increase in the size or number of lytic bone lesions.


Enrollment: 74
Study Start Date: May 2008
Estimated Study Completion Date: January 2017
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Drug Therapy
Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles. To determine the MTD of the combination of Revlimid, Velcade, dexamethasone, and Doxil, four dose levels are planned.
Drug: Lenalidomide
Patients will be treated with Revlimid on days 1-14 in 3-week cycles for 4-8 cycles.
Other Name: Revlimid
Drug: Bortezomib
Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11
Other Name: Velcade
Drug: Dexamethasone
Patients will be treated with Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels.
Drug: Doxil
Patients will be treated with Doxil on day 4.

Detailed Description:

During the Phase I portion of this clinical trial, the doses of Revlimid® and Doxil® will be increased until the best and safest amount (or dose) is identified in combination with Velcade® and Dexamethasone. "Investigational" means that the drug combination is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause and how effective the Velcade®, Doxil®, Dexamethasone and Revlimid® investigational combination is for treating newly diagnosed multiple myeloma. In this clinical trial we are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.

Each of these drugs, Velcade®, Doxil®, Dexamethasone and Revlimid® are approved by the FDA (U.S. Food and Drug Administration). They have not been approved in this combination for use for your type of cancer or any other type of cancer. Velcade® is currently approved by the United States Food and Drug Administration (US FDA) for the treatment of multiple myeloma patients who have received at least one prior therapy. Doxil® has recently been approved by the US FDA for multiple myeloma in combination with Velcade® in patients who have not previously received Velcade® and have received at least one prior therapy. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Revlimid® is currently approved by the US FDA in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

After the Phase I clinical trial defines the safest doses of Velcade®, Doxil®, Dexamethasone and Revlimid® that can be taken together, the research study will move on to its second portion, a Phase II clinical trial. The Phase II portion of the clinical trial will test the clinical effectiveness of the best dose combination of the four drugs.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • At least 18 years of age at the time of consent
  • Measurable disease
  • All necessary baseline studies completed
  • LVEF (left ventricular ejection fraction) greater than or equal to 50 percent by MUGA (multigated acquisition scan) or ECHO (echocardiogram)
  • Must be able to adhere to study visit schedule

Exclusion

  • Greater than or equal to grade 2 peripheral neuropathy on clinical examination within 14 days of enrollment
  • Renal insufficiency
  • Evidence of mucosal or internal bleeding and/ or platelet refractory.
  • Absolute neutrophil count less than 1000 cells/mm^2 within 14 days of enrollment.
  • Acceptable labs
  • Concomitant medications that include corticosteroids
  • Myocardial infarction within 6 months prior to enrollment, uncontrolled angina, severe uncontrolled ventricular arrhythmias
  • Clinically relevant active infection or serious medical condition that places the subject at unacceptable risk
  • Any condition, including laboratory values that places the subject at an unacceptable risk
  • Another malignancy within 3 years of enrollment, with the exception of the complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy
  • Hypersensitivity to bortezomib, boron, or mannitol or any of the components of DOXIL
  • Female subject that is pregnant or breastfeeding.
  • Can not have received any other investigational drugs within 14 days of enrollment
  • Serious medical or psychiatric illness
  • Uncontrolled diabetes mellitus
  • Hypersensitivity to acyclovir or similar antiviral drug
  • POEMS (plasma cell dyscrasia with polyneuropathy)
  • Known HIV
  • Known hepatitis B or C
  • Known intolerance to steroid therapy
  • Known hypersensitivity to required prophylactic mediations
  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: NCT00724568

Locations
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
United States, Illinois
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana Farber Cancer Institute (and Massachusetts General)
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Moshe Talpaz, MD University of Michigan Cancer Center
  More Information

Publications:
Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00724568     History of Changes
Other Study ID Numbers: UMCC 2007.098  HUM 12962 
Study First Received: April 11, 2008
Results First Received: September 3, 2014
Last Updated: June 14, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
Newly Diagnosed Multiple Myeloma

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
Liposomal doxorubicin
Bortezomib
Doxorubicin
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on December 08, 2016