Thalidomide for Multiple Myeloma

This study attempts to examine the potential efficacy of thalidomide in the treatment of
patients with previously untreated multiple myeloma. The trial focuses on patients with
asymptomatic and indolent disease who do not require immediate chemotherapy. We intend to
treat asymptomatic patients with an initial dose of 200 mg each evening, increasing to a
maximum of 800 mg.

Thalidomide is supplied as 50 mg capsules to be taken by mouth. The initial dose will be 200
mg at bedtime daily for 14 days (days 1-14), followed by an increase to 400 mg daily for 14
days (days 15-28), 600 mg daily for 14 days (days 29-42), up to a maximum 800 mg (days
43-completion) daily provided there are no side effects.

Patients who experience significant toxicity (grade 2 or more) at any time during therapy
will receive a lower dose after treatment is interrupted for at least 2 days.

Once a maximum tolerated dose has been reached free of side effects, that dose will be
continued for a total of 3 months from institution of therapy before definition of response
or resistance. Only patients who have received at least 200 mg/d for at least 2 months will
be considered evaluable for response. For patients in remission, treatment will be continued
at the maximum dose free of side effects until relapse. Selected patients <55 years of age
who achieve remission may be eligible for stem cell transplant (SCT) in which case
thalidomide will be discontinued prior to SCT.

Patients must be willing to return for evaluation every 4 weeks since thalidomide may only be
prescribed for 28 day intervals.

- Previously untreated patients with multiple myeloma and without serious or imminent
complications (e.g. impending pathologic fracture, hypercalcemia, renal
insufficiency). All asymptomatic patients with low or intermediate tumor mass will
qualify.

- Patients with high tumor mass, symptomatic or impending fractures, hypercalcemia
(corrected calcium >11.5 mg%), anemia (Hgb <8.5 gm/dl), renal failure (creatinine >2.0
mg/dl), high serum lactate dehydrogenase (>300 U/L) or plasma cell leukemia (>1000/ul)
are ineligible.

- Overt infections or unexplained fever should be resolved before treatment. Adequate
liver function (including SGPT, bilirubin and LDH) is required.

- Patients must have Zubrod performance of 1 or less.

- Patients must provide written informed consent indicating that they are aware of the
investigational nature of this study.

- Life expectancy should exceed 1 year.

- Patients with idiopathic monoclonal gammopathy and non-secretory multiple myeloma are
ineligible. Patients whose only prior therapy has been with local radiotherapy,
alpha-IFN, or ATRA are eligible. Patients exposed to prior high-dose glucocorticoid or
alkylating agent are not eligible.