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

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ClinicalTrials.gov Identifier: NCT00724568
Recruitment Status : Completed
First Posted : July 29, 2008
Results First Posted : September 10, 2014
Last Update Posted : June 2, 2017
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Tracking Information
First Submitted Date  ICMJE April 11, 2008
First Posted Date  ICMJE July 29, 2008
Results First Submitted Date  ICMJE September 3, 2014
Results First Posted Date  ICMJE September 10, 2014
Last Update Posted Date June 2, 2017
Study Start Date  ICMJE May 2008
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2014)
Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) [ Time Frame: 1 month post treatment ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2008)
Determine the MTD of combination therapy with Revlimid, VELCADE, Dexamethasone, and Doxil, (RVDD) and to evaluate the very good partial response rate (CR/nCR+VGPR). [ Time Frame: 8 Cycles ]
Change History Complete list of historical versions of study NCT00724568 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
The Percentage of Patients That Achieved Partial or Complete Response to Treatment. [ Time Frame: 24 weeks (8, 21-day cycles) ]
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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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.
Interventions:
  • Drug: Lenalidomide
  • Drug: Bortezomib
  • Drug: Dexamethasone
  • Drug: Doxil
Publications * Jakubowiak AJ, Griffith KA, Reece DE, Hofmeister CC, Lonial S, Zimmerman TM, Campagnaro EL, Schlossman RL, Laubach JP, Raje NS, Anderson T, Mietzel MA, Harvey CK, Wear SM, Barrickman JC, Tendler CL, Esseltine DL, Kelley SL, Kaminski MS, Anderson KC, Richardson PG. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial. Blood. 2011 Jul 21;118(3):535-43. doi: 10.1182/blood-2011-02-334755. Epub 2011 May 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 3, 2014)
74
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2008)
78
Actual Study Completion Date  ICMJE September 3, 2014
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00724568
Other Study ID Numbers  ICMJE UMCC 2007.098
HUM 12962 ( Other Identifier: University of Michigan IRBMED )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Michigan Rogel Cancer Center
Study Sponsor  ICMJE University of Michigan Rogel Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Moshe Talpaz, MD University of Michigan Rogel Cancer Center
PRS Account University of Michigan Rogel Cancer Center
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP