Trial Information

A Randomized Phase III Study On The Effect Of Thalidomide Combined With Adriamycin, Dexamethasone (AD) And High Dose Melphalan In Patients With Multiple Myeloma

OBJECTIVES:

- Compare the efficacy of doxorubicin, dexamethasone, and high-dose melphalan with versus
without thalidomide, in terms of event-free survival, of patients with multiple
myeloma.

- Determine the response rate, complete response rate, overall survival, and
progression-free survival of patients treated with these regimens.

- Determine the safety and toxicity of thalidomide in combination with intensive
chemotherapy in these patients.

- Assess the value of prognostic factors at diagnosis in individual patients treated with
these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center and treatment policy (1 course vs 2 courses of high-dose melphalan).
Patients are randomized to 1 of 2 treatment arms.

Arm I:

- Patients receive induction chemotherapy (AD) comprising doxorubicin IV on days 1-4 and
oral dexamethasone on days 1-4, 9-12, and 17-20. Patients receive oral thalidomide
daily beginning on day 1 and continuing until 2 weeks before start of stem cell
mobilization. Treatment repeats every 28 days for 3 courses in the absence of disease
progression or unacceptable toxicity.

- Patients receive stem cell mobilization with chemotherapy comprising cyclophosphamide
IV on day 1 and doxorubicin IV and oral dexamethasone on days 1-4 (CAD). Patients also
receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until
last apheresis.

- Beginning 8-10 weeks after stem cell collection, patients receive low-dose oral
thalidomide daily and high-dose melphalan IV on days -3 and -2 as intensification.
Patients undergo stem cell infusion on day 0. Patients may receive a second course of
high-dose melphalan 2-3 months after the first course, in which case, stem cell
infusion follows the second course of melphalan.

- Patients receive maintenance therapy with oral thalidomide daily until disease
progression or after 3 months if no response.

- Beginning 2 months after the last course, patients with an HLA-identical sibling donor
undergo nonmyeloablative stem cell transplantation after radiotherapy.

Arm II:

- Patients receive induction chemotherapy (VAD) comprising vincristine IV and doxorubicin
IV on days 1-4 and dexamethasone on days 1-4, 9-12, and 17-20. Treatment repeats every
28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

- Patients receive stem cell mobilization with CAD chemotherapy as in arm I. G-CSF is
given as in arm I.

- Patients receive high-dose melphalan and undergo stem cell infusion as in arm I.

- Patients receive maintenance therapy with interferon alfa SC 3 times weekly until
progression or after 3 months if no partial response.

- Beginning 2 months after the last course, patients with an HLA-identical sibling donor
undergo nonmyeloablative stem cell transplantation after radiotherapy.

All patients are followed every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this
study within 4 years.