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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Thalidomide
* Drug: Dexamethasone
* Drug: DOXIL


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Thalidomide + dexamethasone<br> | Drug: Thalidomide<br>* 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.<br>Drug: Dexamethasone<br>* Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.<br>|
| Experimental: Thalidomide + dexamethasone + DOXIL<br> | Drug: Thalidomide<br>* 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.<br>Drug: Dexamethasone<br>* Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.<br>Drug: DOXIL<br>* DOXIL 40 mg/m2 will be administered iintravenously (into a vein) on Day 1.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, Newly diagnosed multiple myeloma, Thalidomide, Dexamethasone, DOXIL, Pegylated liposomal hydrochloride doxorubicin injection