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

Multiple Myeloma Clinical Trial

— RVDD  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00724568
• Other study ID #: UMCC 2007.098
• Secondary ID: HUM 12962
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: April 11, 2008
• Last updated: June 9, 2015
• Start date: May 2008
• Est. completion date: January 2017

Study information

• Verified date: June 2015
• Source: University of Michigan Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: January 2017
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• You will be eligible to participate in this study if you are at least 18 years old and have newly diagnosed multiple myeloma.

• You will have blood tests and other screening tests before you are enrolled and your test results must be within the limits outlined for eligibility to participate in this experimental study.

Exclusion Criteria:

• Chronic obstructive or chronic restrictive pulmonary disease and cirrhosis.

• Patient has hypersensitivity to bortezomib, boron or mannitol or any of the components of DOXIL.

• Female subject is pregnant or breast-feeding.

• Patient has received other investigational drugs with 14 days before

• Uncontrolled diabetes mellitus.

• Hypersensitivity to acyclovir or similar anti-viral drug.

• Known HIV infection.

• Known active hepatitis B or C viral infection.

• Known intolerance to steroid therapy.

• Known hypersensitivity to required prophylactic medications.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide
Patients will be treated with Revlimid on days 1-14 in 3-week cycles for 4-8 cycles.
• Bortezomib
Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11
• Dexamethasone
Patients will be treated with Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels.
• Doxil
Patients will be treated with Doxil on day 4.

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Dana Farber Cancer Institute (and Massachusetts General)	Boston	Massachusetts
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	The Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Cancer Center

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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, Richa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD)	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	1 month post treatment	Yes
Secondary	The Percentage of Patients That Achieved Partial or Complete Response to Treatment.	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.	24 weeks (8, 21-day cycles)	Yes