A Study Evaluating Efficacy, Toxicity, Harvest Yield and Quality of Life

Study Overview
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Brief Summary
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Four monthly treatments with pegylated liposomal doxorubicin, thalidomide and dexamethasone for newly diagnosed myeloma patients as induction therapy prior to high dose chemotherapy and autologous stem cell transplant.

Detailed Description
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Multiple myeloma (MM) is an incurable hematological malignancy of plasma cell origin. Plasma cell clonality and dysfunctional immunoglobulin production characterize the disease. The consequences of abnormal plasma cell growth are manifested by a myriad of symptoms and signs that often have significant impact on the patient's quality of life. These include pancytopenia secondary to predominant distribution of tumor cells within the bone marrow along with many other effects. This study is focused on the efficacy of Doxil® (pegylated liposomal doxorubicin) with low dose Dexamethasone and Thalidomide (Ddt) in previously untreated patients with multiple myeloma.

Official Title
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Doxil® (Pegylated Liposomal Doxorubicin), Dexamethasone Plus Thalidomide (Ddt) in Previously Untreated Multiple Myeloma: A Study Evaluating Efficacy, Toxicity, Harvest Yield and Quality of Life

Conditions
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Multiple Myeloma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with active, symptomatic multiple myeloma without prior chemotherapy: Durie-Salmon Stage II-III A/B Stage I patients with at least 2 of the poor prognostic indicators may be eligible. Patients with plasma cell leukemia Non-secretory multiple myeloma patients are eligible Patients between the ages of 18 and 75 years old Female Patients of child bearing age (up to age 50) who are not pregnant and agree to use two adequate birth control methods during the study and at least six months after treatment unless patient has undergone hysterectomy or has been in menopause for 2 years. Patients with Southwest Oncology Group (SWOG) performance status of 3 or better Patients who have received prior lower dose Dexamethasone Therapy (ie. 4 mg QID) as adjunct to radiation therapy for cord compression may be eligible All patients must have a MUGA scan indicating a left ventricular ejection fraction (LVEF) of greater than or equal to 50% within 42 days prior to registration Must be able to understand English. Must be willing and eligible to sign up for the STEPS program Exclusion Criteria: Nursing mothers or women who are pregnant Patients with a history of hypersensitivity reaction to doxorubicin or agents in Doxil® Patients with previous malignancies at other sites except surgically treated nonmelanomatous skin cancers, prostate cancer or superficial cervical cancers, or other cancer from which the patient had been disease free for 5 or more years. History of mediastinal radiation for any reason History of receiving prior anthracyclines Patients with uncontrolled medical problems such as diabetes mellitus, cardiac, pulmonary, hepatic, and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma Myocardial infarction within 6 months of enrollment in the study. Major surgery within 4 weeks of enrollment. Patients previously treated or receiving other treatment for multiple myeloma other than lower doses dexamethasone as adjunct to radiotherapy Pre-existing peripheral neuropathy Patients with previously diagnosed malabsorption syndromes or anatomical abnormalities of the gastrointestinal tract that result in malabsorption syndromes. Patients with a history of cardiac disease, defined as New York Heart Association Class II or greater, or clinical evidence of congestive heart failure. Patients with psychiatric or central nervous systems disorders interfering with compliance of orally administered medication. Patients currently receiving anticoagulant therapy for venous thromboembolic episode or other hypercoagulable states. Patients who are unable to understand the English language.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Doxil, Thalidomide, Dexamethasone | Drug: Doxil<br>* Doxil 40 mg/m2 IV day 1<br>* Other names: pegylated liposomal doxorubicin;Drug: Thalidomide<br>* 50-100 mg day 1-28<br>* Other names: thalidomid;Drug: Dexamethasone<br>* Dexamethasone 40 mg day 1-4 and 15-18<br>* Other names: decadron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Response rate after completion of first cycle. Measured as the proportion of subjects who have a partial response (PR) or complete response (CR), represented as the overall response rate (ORR). SWOG/IBMTR (Southwest Oncology Group/International Blood and Marrow Transplant Research) criteria utilized to determine multiple myeloma response rates. | At End of Cycle 1, 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Count of Participants with adverse events. | End of study, up to 12 months |