Thalidomide + Dexamethasone vs. DOXIL (Doxorubicin HCl Liposome Injection) + Thalidomide + Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

Condition(s) targeted: Multiple Myeloma; Cancer

Intervention: DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Official(s) and/or principal investigator(s):
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

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

Official title: 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

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Complete response rate defined as the proportion of patients who achieve a complete response. This is assessed at the beginning of every treatment cycle prior to treatment starting at Cycle 2. Complete response must be maintained for at least 6 weeks.

Secondary outcome: Overall response, time to 1st response and time to progression, assessed as above. Overall survival defined as time period from enrollment until death. Achievement of successful engraftment after bone marrow transplant.

Detailed description: The established treatment for newly diagnosed multiple myeloma is vincristine + adriamycin + intermittent high-dose dexamethasone therapy, but it requires a 96-hour continuous infusion of conventional doxorubicin. Newer options can be administered in an out-patient setting, which is more convenient for patients. However, the optimal regimen in producing a high rate of complete response and durable response remains to be established. This is a multi-center, open-label, randomized (patients are assigned different treatment sbased on chance) study to compare the safety and effectiveness of Thalidomide + Dexamethasone vs. DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone in patients with newly diagnosed multiple myeloma. Treatments are administered in 28-day cycles. Patients will receive 4-12 cycles, depending on the response of their multiple myeloma to the treatment they receive (measured according to the European Group for Blood and Marrow Transplant Response Criteria). Thalidomide + Dexamethasone treatment is as follows: Thalidomide by mouth every night without food on Days 1-28. Dosing will be gradually increased during Cycle 1: 50 mg on Days 1-7, 100 mg on Days 8-14, 150 mg on Days 15-21, and 200 mg on Days 22-28. Thereafter, 200 mg daily will be administered for all subsequent cycles. Dexamethasone will be given at 40 mg by mouth on Days 1-4, Days 9-12 and Days 17-20. DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone treatment is as follows: Thalidomide and Dexamethasone will be administered in the same way as described for the Thalidomide + Dexamethasone treatment group. DOXIL (doxorubicin HCl liposome injection) will be administered on Day 1 via intravenous infusion of 40 mg/m2 over 60 minutes (Cycle 1 infusion is over 90 minutes). Patients will be assessed for safety and efficacy by standard evaluations for patients with multiple myeloma at each cycle. 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) . The study hypothesis is that the DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone treatment will be more effective in the treatment of newly diagnosed multiple myeloma than the Thalidomide + Dexamethasone treatment, as measured by number of complete responses and will be generally well-tolerated.

Specific dose adjustments can be made to Thalidomide and/or DOXIL (doxorubicin HCl liposome injection) based upon toxicity. Maximum duration of study participation for patients would be 48 weeks.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 < 45%

- No history of life-threatening thromboembolic events of any kind (i. e., 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

For FDA Approved Product labeling, refer to the following link:http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

Additional information is provided at the following link;http://dailymed.nlm.nih.gov/dailymed/about.cfm

For FDA Safety Alerts and Recalls refer to the following link:www.fda.gov/MEDWATCH/safety.htm

Starting date: November 2004
Last updated: February 28, 2008