Clinical trial NCT00215943: Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: hematologic malignancy
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2005-09-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigators planned to accrue 176 participants, to compare 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). Investigators also planned to test if treatment with zoledronate immediately prior to chemotherapy results in an enhanced response to treatment (i.e. increase in complete response rates).

Detailed description: Patients Randomized to receive VAD (vincristine, adriamycin, dexamethasone): All patients received four cycles of VAD repeated every 4 weeks. Chemotherapy was administered by continuous IV Infusion for 96 hours: vincristine at a dose of 0.4 mg/day and doxorubicin at a dose of 9 mg/m\^2/day. Patients were administered dexamethasone 40 mg by mouth (PO) on days 1 to 4, 9 to 12, and 17 to 20 of the initial two cycles. Dexamethasone was given only on days 1-4 of all subsequent cycles. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle. This schedule continued monthly as long as the patient remained on study. The dose was calculated based on the patients' monthly creatinine clearance. Upon initiation of Zometa therapy, the following guidelines were applied: For patients with creatinine clearance \>60 mL/min, the recommended dose remained at 4mg. For patients with reduced creatinine clearance, dosing was calculated to achieve the same area under curve (AUC) as in patients with creatinine clearance of 75 mL/min. Creatinine clearance was calculated using the Cockcroft-Gault formula.

Eligibility criteria: 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) or serum aspartate aminotransferase (AST) \> 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

Primary outcomes:
measure: Response Rates of VAD vs. Thalidomide/Dexamethasone
timeFrame: End of Cycle 4 - 4 Months per Participant
Secondary outcomes:
measure: Number of Participants With Adverse Events, by Group
timeFrame: 4 Years, 7 Months
measure: Number of Participants With Progression Free Survival (PFS), by Treatment Arm
timeFrame: 4 Months
measure: Overall Survival (OS), by Treatment Arm
timeFrame: Up to 10 Years
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic
state: Florida
city: Port Charlotte
country: United States
facility: Fawcett Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: San Juan
country: Puerto Rico
facility: San Juan VA Hospital
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Melissa Alsina, MD
role: PRINCIPAL_INVESTIGATOR
References: