Romiplostim in Increasing Low Platelet Counts in Patients With Multiple Myeloma Receiving Chemotherapy

PRIMARY OBJECTIVES:

I. To determine if Nplate (romiplostim) is capable of increasing platelet counts to > 50 x
10^9/L for greater than 2 weeks in myeloma patients with chemotherapy induced
thrombocytopenia.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of romiplostim in this patient population by standard Common
Toxicity Criteria (CTC).

II. To determine any increase in thrombosis or marrow fibrosis.

OUTLINE:

Patients receive romiplostim subcutaneously (SC) once weekly for up to 6 weeks. Patients
achieving a platelet count > 50 x 10^9 then receive romiplostim once weekly during 1 course
of chemotherapy and may continue for as long as benefit is seen.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care

- Subject is not pregnant or breast feeding, and cannot become pregnant within 30 days
after the end of treatment

- Female subject of child bearing potential must be willing to use, in combination with
her partner, 2 forms highly effective contraception during treatment and for 1 month
after the end of treatment

- Diagnosis of any stage of multiple myeloma based on standard criteria as follows:

- Major criteria

1. Plasmacytomas on tissue biopsy

2. Bone marrow plasmacytosis (> 30% plasma cells)

3. Monoclonal immunoglobulin spike on serum electrophoresis (immunoglobin G
[IgG] > 3.5 G/dL or immunoglobin A [IgA] > 2.0 G/dL) or kappa or lambda
light chain excretion > 1 G/day on 24 hour urine protein electrophoresis

- Minor criteria

1. Bone marrow plasmacytosis (10 to 30% plasma cells)

2. Monoclonal immunoglobulin present but of lesser magnitude than given under
major criteria

3. Lytic bone lesions

4. Normal immunoglobin M (IgM) < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

- Any of the following sets of criteria will confirm the diagnosis of multiple
myeloma:

- Any two of the major criteria

- Major criterion 1 plus minor criterion b, c, or d

- Major criterion 3 plus minor criterion a or c

- Minor criteria a, b and c or a, b and d

- Karnofsky performance status >= 50

- Platelet count =< 50 x 10^9/L untransfused of at least 2 weeks duration, secondary to
prior chemotherapy. If there is a platelet count of > or = 50 x 10(9)/L after a
transfusion, that value will be discounted.

This may include a combination regimen including lenalidomide; these regimens will include
dexamethasone, cyclophosphamide, etoposide, cisplatin (DCEP), Velcade with Doxil, Cytoxan
and/or lenalidomide; patients who have thrombocytopenia (CIT) from lenalidomide or from
radiation therapy alone will not be allowed

- Calculated or measured creatinine clearance >= 30 mL/min

Exclusion Criteria:

- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein [M-protein] and skin changes)

- Plasma cell leukemia

- Receiving steroids daily for other medical conditions, e.g., asthma, systemic lupus
erythematosus, rheumatoid arthritis

- Infection not controlled by antibiotics

- Human immunodeficiency virus (HIV) infection; patients should provide consent for HIV
testing according to the institution's standard practice

- Known active hepatitis B or C

- Patient had myocardial infarction within 6 months prior to enrollment, New York
Hospital Association (NYHA) class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities; prior to study entry, any
electrocardiogram (ECG) abnormality at screening must be documented by the
investigator as not medically relevant

- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

- Other serious medical or psychiatric illness that could potentially interfere with the
completion of treatment according to this protocol

- Female subject is pregnant or lactating; confirmation that the subject is not pregnant
must be established by a negative serum beta-human chorionic gonadotropin (hCG)
pregnancy test result obtained during screening; pregnancy testing is not required for
postmenopausal or surgically sterilized women

- Patient has > 1.5 x upper limit of normal (ULN) total bilirubin

- Patients with existing deep venous thrombosis will be excluded

- Patients receiving maintenance therapy with myelosuppressive medications such as
lenalidomide will be excluded