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

NCT ID: NCT00724568

Last Updated: 2017-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2014-09-03

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Patients will be treated with Revlimid on days 1-14 in 3-week cycles for 4-8 cycles.

Bortezomib

Intervention Type: DRUG

Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11

Dexamethasone

Intervention Type: DRUG

Patients will be treated with Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels.

Doxil

Intervention Type: DRUG

Patients will be treated with Doxil on day 4.

Interventions

Lenalidomide

Patients will be treated with Revlimid on days 1-14 in 3-week cycles for 4-8 cycles.

Intervention Type: DRUG

Bortezomib

Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11

Intervention Type: DRUG

Dexamethasone

Patients will be treated with Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels.

Intervention Type: DRUG

Doxil

Patients will be treated with Doxil on day 4.

Intervention Type: DRUG

Other Intervention Names

Revlimid; Velcade

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moshe Talpaz, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

Emory University Hospital

Atlanta, Georgia, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

Dana Farber Cancer Institute (and Massachusetts General)

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

The Ohio State University Medical Center

Columbus, Ohio, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 21596852 (View on PubMed)

Other Identifiers

HUM 12962

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2007.098

Identifier Type: -

Identifier Source: org_study_id