Multiple Myeloma
Conditions
Brief summary
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
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.
Interventions
DRUGDoxil
Doxil 40 mg/m2 IV day 1
DRUGThalidomide
50-100 mg day 1-28
DRUGDexamethasone
Dexamethasone 40 mg day 1-4 and 15-18
Sponsors
Ortho Biotech, Inc.
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | At End of Cycle 1, 28 Days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | End of study, up to 12 months | Count of Participants with adverse events. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Doxil, Thalidomide, Dexamethasone
Doxil: Doxil 40 mg/m2 IV day 1
Thalidomide: 50-100 mg day 1-28
Dexamethasone: Dexamethasone 40 mg day 1-4 and 15-18 | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 2 |
| Overall Study | Removed due to wrong diagnosis | 1 |
| Overall Study | Treatment delays | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Continuous | 61 years |
| Region of Enrollment United States | 25 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 25 |
| other Total, other adverse events | 0 / 25 |
| serious Total, serious adverse events | 8 / 25 |
Outcome results
Primary
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.
Time frame: At End of Cycle 1, 28 Days
Population: Five subjects did not complete first cycle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Overall Response Rate | 95 percentage of participants |
Secondary
Toxicity
Count of Participants with adverse events.
Time frame: End of study, up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 | Toxicity | 10 Participants |