A Pilot, Phase-I Trial of Rabbit Anti-Thymocyte Globulin (rATG, Thymoglobulin™) in Combination With Rapamycin in Relapsed Multiple Myeloma (MM)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Previously diagnosed multiple myeloma (MM) based on standard criteria

- Soft tissue (not bone only) plasmacytomas allowed

- Measurable disease, meeting both of the following criteria:

- Monoclonal population of plasma cell in the bone marrow

- Quantifiable serum and/or urine monoclonal protein (i.e., generally, but not
exclusively, IgG > 1 g/dL, IgA > 0.5 g/dL, or urine light-chain excretion ≥ 200
mg/24 hours)

- Steroid-refractory disease, defined as less than a minimum response to prior
high-dose glucocorticoid therapy

- Minimal response requires all of the following criteria:

- 25-49% reduction in the level of serum monoclonal paraprotein maintained
for ≥ 6 weeks

- 50-89% reduction in 24-hour urinary light-chain excretion, but still > 200
mg/24 hours, maintained for ≥ 6 weeks

- 25-49% reduction in the size of soft tissue plasmacytomas (clinically or by
CT scan or MRI)

- No increase in size or number of lytic bone lesions

- High-dose glucocorticoid therapy defined as 480 mg dexamethasone (or equivalent)
alone or as part of a vincristine, doxorubicin, and dexamethasone regimen

- Must have undergone autologous transplantation OR received ≥ 2 conventional lines of
therapy

- Currently requiring therapy for progressive disease, as indicated by any of the
following criteria:

- 25% increase in paraprotein

- Development of new or progression of pre-existing lytic bone lesions or soft
tissue plasmacytomas

- Hypercalcemia not attributable to any other cause

- Relapse from complete remission

- No nonsecretory MM

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-2

- 3-4 allowed if, in the opinion of the investigator, secondary to MM-related bone
pain

- Life expectancy ≥ 3 months

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Bilirubin ≤ 1.5 times ULN

- Calcium < 14 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- Hepatitis B surface antigen and hepatitis C antibody negative

- No known history of allergy to rabbit proteins

- No history of cardiac amyloidosis

- No poorly controlled hypertension, diabetes mellitus, coronary artery disease, or
other serious medical or psychiatric illness

- No myocardial infarction within the past 6 weeks

- No New York Heart Association class III or IV heart failure

- No uncontrolled angina

- No severe uncontrolled ventricular arrhythmias

- No evidence of acute ischemia or active conduction system abnormality by
electrocardiogram

- No active systemic infection requiring treatment unless adequately controlled with
appropriate antimicrobial therapy (e.g., treated central line infection)

- No acute viral illness

- No pathologic fractures or symptomatic hyperviscosity

- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer, cervical cancer in situ, or any other cancer with a disease-free status for ≥
3 years

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 8 weeks since prior immunotherapy or antibody therapy

- At least 4 weeks since prior major surgery (except for kyphoplasty)

- At least 3 weeks since prior conventional chemotherapy or radiotherapy for MM

- At least 3 weeks since prior bortezomib, thalidomide, or clarithromycin for MM

- No prior anti-thymocyte globulin

- No concurrent radiotherapy

- No other concurrent antineoplastic therapy with known activity against MM, including
clarithromycin

- No other concurrent investigational agents