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

Study Overview
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Brief Summary
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This phase II trial studies how well romiplostim works in increasing low platelet counts in patients with multiple myeloma receiving chemotherapy. Romiplostim may cause the body to make platelets after chemotherapy

Detailed Description
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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.

Official Title
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Phase II Trial Evaluating the Efficacy and Safety of Romiplostim (Nplate) Treatment of Chemotherapy Induced Thrombocytopenia in Patients With Multiple Myeloma

Conditions
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Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma, Thrombocytopenia

Intervention / Treatment
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* Biological: romiplostim


Participation Criteria
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Eligibility Criteria
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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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care Subject is not pregnant or breast feeding, and cannot become pregnant within 30 days after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 Plasmacytomas on tissue biopsy Bone marrow plasmacytosis (> 30% plasma cells) 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 Bone marrow plasmacytosis (10 to 30% plasma cells) Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria Lytic bone lesions 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive care (romiplostim)<br>Patients receive romiplostim 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.. | Biological: romiplostim<br>* Given SC<br>* Other names: Nplate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Have Responded | Response is defined as platelet increases to greater than 50 x 10^9/L for more than 2 weeks. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Experienced Thrombosis or Marrow Fibrosis |  | Up to 1.5 years |