A Study of Thalidomide Plus Dexamethasone (Thal-Dex) Versus DOXIL plusThalidomide Plus Dexamethasone (DOXIL -Thal-Dex) in Patients With Newly Diagnosed Multiple Myeloma

A Randomized, Open-Label, Multi-Center Trial Comparing Thalidomide Plus Dexamethasone (Thal-Dex) Versus DOXIL plusThalidomide Plus Dexamethasone (DOXIL -Thal-Dex) in Subjects With Newly Diagnosed Multiple Myeloma

The purpose of this study is to determine if Thalidomide + Dexamethasone or DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone is more effective in treating newly diagnosed patients with multiple myeloma. The number of patients whose multiple myeloma disappears for a period of time (complete Response) will be studied to make the determination of which treatment is more effective.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Thalidomide; Drug: Dexamethasone; Drug: DOXIL

Detailed Description

This is a multi-center, open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance) study to compare the safety and effectiveness of Thalidomide + Dexamethasone versus DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone in patients with newly diagnosed multiple myeloma. Treatments are administered in 28-day cycles. Patients will receive 4 to 12 treatment cycles, depending on the response of their multiple myeloma to the treatment (measured according to the European Group for Blood and Marrow Transplant Response Criteria). Patients will have additional tests that include Multiple Gated Acquisition (MUGA) scans or echocardiograms to assess the patients for potential cardiotoxicity that could be related to treatment with DOXIL (doxorubicin HCl liposome injection). Maximum duration of study participation for each participant will be 48 weeks.

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Fountain Valley, California, United States
    • Greenbrae, California, United States
    • La Verne, California, United States
    • Los Angeles, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Connecticut
    • New London, Connecticut, United States
  • Florida
    • Boca Raton, Florida, United States
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
    • Orange City, Florida, United States
    • Ormond Beach, Florida, United States
  • Georgia
    • Lawrenceville, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Kansas
    • Wichita, Kansas, United States
  • Maryland
    • Baltimore, Maryland, United States
    • Bethesda, Maryland, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
    • St Louis Park, Minnesota, United States
  • Missouri
    • Columbia, Missouri, United States
    • Kansas City, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Jersey
    • Englewood, New Jersey, United States
    • Hackensack, New Jersey, United States
    • Jersey City, New Jersey, United States
    • Voorhees, New Jersey, United States
  • New York
    • Albany, New York, United States
    • Armonk, New York, United States
    • Box 302, New York, United States
    • Bronx, New York, United States
    • Brooklyn, New York, United States
    • Nyack, New York, United States
    • Valhalla, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
    • Winston Salem, North Carolina, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
    • Tulsa, Oklahoma, United States
  • Oregon
    • Eugene, Oregon, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
    • Wynnewood, Pennsylvania, United States
  • South Carolina
    • Columbia, South Carolina, United States
    • Easley, South Carolina, United States
    • Sumter, South Carolina, United States
  • Tennessee
    • Memphis, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Bedford, Texas, United States
    • Dallas, Texas, United States
    • Fort Worth, Texas, United States
    • Fredericksburg, Texas, United States
    • Houston, Texas, United States
  • Vermont
    • Burlington, Vermont, United States
  • Virginia
    • Fairfax, Virginia, United States
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States
  • Washington
    • Spokane, Washington, United States
    • Vancouver, Washington, United States
    • Yakima, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previously untreated, histologically confirmed multiple myeloma (per International Myeloma Working Group [IMWG] criteria
• Eastern Cooperative Oncology Group (ECOG) status 0-2
• Adequate absolute neutrophil count (ANC), platelet count and hemoglobin
• Adequate serum calcium
• Enrollment in System for Thalidomide Education and Prescribing Safety Program (S.T.E.P.S.)

Exclusion Criteria:

• No treatment with dexamethasone for multiple myeloma
• No peripheral neuropathy of Grade 2 or higher
• No Left Ventricular Ejection Fraction (LVEF) of less than 45 percentage
• No history of life-threatening thromboembolic events of any kind (ie, myocardial infarction, pulmonary embolism, stroke or others), within 1 year before enrollment in the study
• No deep vein thrombosis (DVT) within 1 year of enrollment
• No current anticoagulation for DVT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thalidomide + dexamethasone	Drug: Thalidomide; Participants will receive thalidomide orally every night (at bedtime) without food on days 1-28 and dosing will gradually increase during Cycle 1 starting at 50 mg on 1 to 7 days, 100 mg on 8 to 14 days, 150 mg on 15 to 21 days, and 200 mg 22 to 28 days. Thalidomide 200 mg per day will be administered for subsequent cycles. Participants will receive thalidomide for minimum of 4 cycles and a maximum of 12 cycles.; Drug: Dexamethasone; Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.
Experimental: Thalidomide + dexamethasone + DOXIL	Drug: Thalidomide; Participants will receive thalidomide orally every night (at bedtime) without food on days 1-28 and dosing will gradually increase during Cycle 1 starting at 50 mg on 1 to 7 days, 100 mg on 8 to 14 days, 150 mg on 15 to 21 days, and 200 mg 22 to 28 days. Thalidomide 200 mg per day will be administered for subsequent cycles. Participants will receive thalidomide for minimum of 4 cycles and a maximum of 12 cycles.; Drug: Dexamethasone; Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.; Drug: DOXIL; DOXIL 40 mg/m2 will be administered iintravenously (into a vein) on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate: Number of Participants Who Achieved a Complete Response	Complete response rate to study medication is defined as number of participants who acheived complete response by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions. Complete response was assessed at the beginning of every treatment cycle prior to treatment, starting at Cycle 2.	From Cycle 2 until 28 days following completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR)	Overall response to study medication is defined as number of participants who acheived a complete response (CR) or partial response (PR) by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.	From Cycle 2 until 28 days following completion of treatment
Time to 1st Response	Time to first response was defined as the interval from date of randomization to date of achieving a partial response (PR) or better according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.	From Cycle 2 until 28 days following completion of treatment
Time to Progression	Time to progression is the interval between the date of randomization until disease progression or death due to progression.	From randomization until death or as assessed up to 2 years post last participant last treatment visit
Overall Survival: Number of Participants Died Due to Any Cause		From randomization until death or as assessed up to 2 years post last participant last treatment visit
Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow)		From randomization until death or as assessed up to 2 years post last participant last treatment visit
Engraftment: Number of Participants Who Underwent Engraftment	Engraftment is the process of transplanted stem cells reproducing new cells.	From randomization until death or as assessed up to 2 years post last participant last treatment visit

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: December 1, 2004
• First Submitted That Met QC Criteria: December 1, 2004
• First Posted (Estimate): December 2, 2004

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: February 20, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Thalidomide; Multiple myeloma; Dexamethasone; Newly diagnosed multiple myeloma; DOXIL; Pegylated liposomal hydrochloride doxorubicin injection
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Thalidomide
• Other Study ID Numbers: CR004579; DO04-23-006 (Other Identifier: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.)