Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)
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Purpose
This study compares the response rate, overall response rate and survival of patients with multiple myeloma (MM) when randomized to two regimens (thalidomide+Dexamethasone versus Vincristine+Adriamycin+Dexamethasone). This study also is testing if treatment with zoledronate immediately prior to chemotherapy results in an enhanced response to treatment (i.e. increase in complete response rates).
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma |
Drug: zoledronic acid Drug: dexamethasone Drug: thalidomide Drug: vincristine Drug: adriamycin |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase III Randomized Trial of Thalidomide/Dexamethasone vs VAD as Induction Chemotherapy for Newly Diagnosed Myeloma Patients and Evaluation of the Effects of Zoledronate on Chemotherapy Induced Apoptosis and Antigen Presentation. |
- Level of Response Observed [ Time Frame: 6 Months or until start of transplant for transplant candidates ] [ Designated as safety issue: No ]Compare response rates of thalidomide/Dexamethasone vs. VAD as induction regimens in newly diagnosed MM. The Blade (15) criteria for remission in multiple myeloma will be used to assess response to VAD and thalidomide/dexamethasone therapy. Any improvement that meets the criteria for complete response (CR), partial response (PR), or minimal response (MR) will be considered a response for the purposes of calculating the primary endpoint. Progressive disease (PD) or relapse from CR will be considered treatment failure in determining the primary endpoint.
- Number of Participants With Adverse Events [ Time Frame: 6 Months or until start of transplant for transplant candidates ] [ Designated as safety issue: Yes ]Compare the toxicities of Thalidomide/Dexamethasone vs. VAD as induction regimens in newly diagnosed MM.
- Number of Participants With Progression Free Survival (PFS) [ Time Frame: 6 Months or until start of transplant for transplant candidates ] [ Designated as safety issue: No ]Compare the effects of induction thalidomide/Dexamethasone vs. VAD with respect to progression free survival in newly diagnosed MM.
- Number of Participants With Overall Survival (OS) [ Time Frame: 6 Months or until start of transplant for transplant candidates ] [ Designated as safety issue: No ]Compare the effects of induction thalidomide/Dexamethasone vs. VAD with respect to overall survival in newly diagnosed MM.
| Enrollment: | 90 |
| Study Start Date: | June 2003 |
| Study Completion Date: | August 2012 |
| Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: VAD Treatment
VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin will be administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients will receive 4 to 6 cycles of therapy. Dexamethasone will be taken in pill form. During the first 2 cycles it will be taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone will be taken only on days 1-4.
|
Drug: zoledronic acid
Patients will be randomized to receive zoledronic acid I.V. on either Day 1 or 15 of each cycle. This schedule will continue monthly as long as the patient remains on study. The dose will be calculated based on the patients' monthly creatinine clearance.
Other Names:
Drug: vincristine
As outlined in VAD Treatment Arm
Other Names:
Drug: adriamycin
As outlined in VAD Treatment arm
Other Names:
|
|
Active Comparator: Thalidomide and Dexamethasone Treatment
Thalidomide will be taken orally once every day in the evening for four to six months. The dexamethasone will be taken in a pill form. During the first 2 cycles it will be taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone will be taken only on days 1-4.
|
Drug: zoledronic acid
Patients will be randomized to receive zoledronic acid I.V. on either Day 1 or 15 of each cycle. This schedule will continue monthly as long as the patient remains on study. The dose will be calculated based on the patients' monthly creatinine clearance.
Other Names:
Drug: dexamethasone
As outlined in VAD Treatment arm and Thalidomide and Dexamethasone Treatment arm
Other Names:
Drug: thalidomide
As outlined in Thalidomide and Dexamethasone Treatment arm
Other Name: Thalomid™
|
Detailed Description:
If the patients are randomized to receive VAD they will have an intravenous catheter inserted. The chemotherapy drugs, vincristine and adriamycin will be administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. The patients will receive 4 to 6 cycles of therapy. The dexamethasone will be taken in a pill form. During the first 2 cycles it will be taken on days 1-4, 9-12, and 17-20. For all other cycles dexamethasone will be taken only on days 1-4.
Patients who are randomized to receive thalidomide and dexamethasone will take thalidomide orally once every day in the evening for 4 to 6 months. The dexamethasone will be taken in a pill form. During the first 2 cycles it will be taken on days 1-4, 9-12, and 17-20. For all other cycles dexamethasone will be taken orally on days 1-4.
The dose of thalidomide will start at 100 mg per day and will be increased slowly to 200 mg over several weeks. All patients taking thalidomide will also be required to comply with the System of Thalidomide Education and Prescribing Safety program (S.T.E.P.S.). This is a program of education and safety related to the use of Thalidomide and the prevention of pregnancy. You will be required to sign a separate consent indicating that they understand and agree with the guidelines. Women of child bearing potential will be required to have a negative pregnancy test within 24 hours of starting thalidomide. This will be repeated every week for 4 weeks and then monthly for the duration of thalidomide therapy. Women with irregular menstruation will have the pregnancy test done every 2 weeks.
All patients will receive zoledronate by intravenous infusion, over at least 15 minutes monthly (either on the first or fifteenth day of each month). The schedule will be randomly selected and the patient will not have a choice on which day you receive the zoledronate.
Supportive medications (all study patients):
During each cycle of therapy, additional medications will be given to help reduce the side effects of treatment. Patients enrolled in this study will be prescribed supportive medications such as: 1) stomach acid suppressors to prevent stomach ulcers, and 2) antibiotics to protect against infections while receiving dexamethasone, 3) "blood thinners" to reduce the development of blood clots. This medicine can be taken as pills or shots under the skin.If the subject will receive VAD then they will be on a preventative dose of blood thinner. If they are to receive thalidomide/dexamethasone you will be on a higher dose of blood thinner. Other medications such as those used to prevent nausea, diarrhea and medications for low blood counts may also be given as needed.
At the end of 4 months, those patients who are eligible, will proceed to have high-dose chemotherapy and stem cell transplantation. These patients will then be taken off active study.
Patients not eligible for transplant will continue with chemotherapy or thalidomide and dexamethasone for 2 additional months (total of 6 months) and will then be taken off active study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must have newly diagnosed MM confirmed by the presence of bone marrow plasmacytosis with > 10 percent plasma cells, sheets of plasma cells, or biopsy-proven plasmacytoma. Patients must have Durie-Salmon Stage IIA-B or IIIA-B. Patients with non-secretory myeloma are eligible. (These patients will not be included in the analysis of response rates, but will be assessed for toxicity and survival).
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2, or 3
- ≥ 18 years of age.
- Signed informed consent form
- Expected survival of greater than 8 weeks
- Capable of swallowing study medication tablets
- Capable of following directions regarding taking study medication, or has a daily care provider who will be responsible for administering study medication.
- Patients will be eligible for study even if they lack socioeconomic access to autologous transplantation. (These patients will be identified prior to randomization so as not to confound study results).
- All patients (in the event that they are randomized to the thalidomide/dexamethasone arm) must agree to take part in the "System for Education and Prescribing Safety" (S.T.E.P.S.)™. They must sign a separate informed consent for this program.
Exclusion Criteria:
- Elevated direct bilirubin > 2 mg/dl
- Serum alanine aminotransferase ( ALT, formerly SGPT) or serum aspartate aminotransferase (AST, formerly SGOT) > 2 times the upper limit of normal (ULN)
- Absolute neutrophil count (ANC) <1000/mL, unless felt to be secondary to myeloma
- Ongoing radiation therapy, or radiation therapy within 3 weeks prior to first treatment, unless the acute side effects associated with such therapy are resolved.
- Prior treatment for multiple myeloma
- Prior bisphosphonate use is allowed but they must be discontinued before starting treatment.
- Concurrent uncontrolled serious infection
- Patients with peripheral (sensory) neuropathy, grade 3 or higher
- Life-threatening illness (unrelated to tumor)
- History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
- Women of childbearing potential (unless utilizing birth control) or who are pregnant or nursing will be excluded from this study.
- Patients with comorbid conditions that would contraindicate the use of vincristine, doxorubicin, dexamethasone, thalidomide, or zoledronate.
- Plasma Cell Leukemia
Contacts and Locations| United States, Florida | |
| Morton Plant Hospital | |
| Clearwater, Florida, United States, 33756 | |
| Watson Clinic | |
| Lakeland, Florida, United States, 33805 | |
| Fawcett Memorial Hospital | |
| Port Charlotte, Florida, United States, 33949 | |
| H. Lee Moffitt Cancer Center & Research Institute | |
| Tampa, Florida, United States, 33612 | |
| Puerto Rico | |
| San Juan VA Hospital | |
| San Juan, Puerto Rico, 00921 | |
| Principal Investigator: | Melissa Alsina, MD | H. Lee Moffitt Cancer Center and Research Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | H. Lee Moffitt Cancer Center and Research Institute |
| ClinicalTrials.gov Identifier: | NCT00215943 History of Changes |
| Other Study ID Numbers: | MCC-13043, CZOL446E |
| Study First Received: | September 15, 2005 |
| Last Updated: | September 13, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
|
hematologic malignancy |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone acetate |
Dexamethasone Dexamethasone 21-phosphate Doxorubicin Thalidomide Vincristine BB 1101 Zoledronic acid Diphosphonates Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 17, 2013