Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma
Intervention: zoledronic acid; dexamethasone; thalidomide; vincristine; adriamycin
Intervention description: Patients were randomized to receive zoledronic acid I.V. 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.; As outlined in VAD Treatment arm and Thalidomide and Dexamethasone Treatment arm; As outlined in Thalidomide and Dexamethasone Treatment arm; As outlined in VAD Treatment Arm; As outlined in VAD Treatment arm
Intervention MeSH terms: Zoledronic Acid; Thalidomide; Dexamethasone; Doxorubicin; Vincristine; Liposomal doxorubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hematologic malignancy

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).
    

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