A Trial of TBL12 Sea Cucumber Extract in Patients With Untreated Asymptomatic Myeloma

Study Overview
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Brief Summary
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This study proposes to determine the clinical activity of this agent in patients with asymptomatic multiple myeloma. It is believed that TBL12 will help delay the onset of active multiple myeloma, with very few-if any- side effects.

Detailed Description
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Multiple myeloma is a cancer that evolves from a state known as Monoclonal Gammopathy of Undetermined Significance (MGUS), defined by parameters of M spike and bone marrow. After evolution to myeloma, patients may be asymptomatic, that is, without any endorgan disease of hypercalcemia, renal insufficiency, anemia or bone lesions. In asymptomatic myeloma (ASxM), there is no standard therapy. Thalidomide has been tried in patients with ASxM but with significant toxicity. The patients with ASxM are evaluable in terms of paraprotein measurements. TBL12 sea cucumber extract has been shown to have a number of antitumor properties preclinically, including antiangiogenesis and direct tumor cytotoxicity. TBL12 has been used by a number of patients as a food supplement without any toxicity detected. The investigators thus propose to determine the clinical activity of this agent in patients with ASxM. Patients will be given TBL12 at the dose of 2 units of 20 mL each twice per day daily until disease progression and the effects on the paraprotein noted. Clinical effects seen will be correlated with any in vitro changes in angiogenesis in patient bone marrow samples. The results of this trial may form the basis for the use of this nontoxic agent in patients with the prodrome of or with other early cancers.

Official Title
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A Phase II Trial of TBL12 Sea Cucumber Extract in Patients With Untreated Asymptomatic Myeloma

Conditions
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Myeloma

Intervention / Treatment
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* Drug: TBL12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma based on standard criteria as follows: Major Criteria Plasmacytomas on tissue biopsy Bone marrow plasmacytosis (> 30% plasma cells) Monoclonal immunoglobulin (Ig) spike on serum electrophoresis (IgG > 3.5 g/dL or IgA > 2.0 g/dL); 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 Normal 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 Major criterion 3 plus minor criterion a or c Minor criteria a, b and c Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours. Non-secretors must have measurable protein by Freelite or measurable disease such as plasmacytoma to be eligible. Has asymptomatic disease, i.e., does not have hypercalcemia, renal insufficiency, anemia or bone lesions. Karnofsky performance status ≥ 80 (See Appendix B) Is infertile (i.e. surgically sterile or 12 months post-menopausal) or is practicing an adequate form of contraception, as judged by the investigator (i.e., birth control pills, double barrier method, abstinence, etc.) Age 18 years or older Has given voluntary written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care. Exclusion Criteria: Prior treatment for myeloma (symptomatic or asymptomatic). POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes) Plasma cell leukemia Patients with a history of thyroid problems. Receiving steroids > the equivalent of 10 mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, 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 New York Hospital Association (NYHA) Class III or IV heart failure or EKG evidence of acute ischemic disease Second malignancy requiring treatment in last 3 years Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol Positive pregnancy test in women of childbearing potential

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sea cucumber extract<br>TBL12 is administered orally at a dose of 2 units (of 20 mL each) twice a day, in 4-week cycles, until disease progression or there is sign of disease progression. | Drug: TBL12<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (All Treated Patients) | Response [complete response (CR), partial response (PR), and stable disease (SD)] was assessed after approximately 2 months, 6 months and then every 4 months, until progression of disease. Response and progression of disease evaluation is based on the criteria reported by Blade, et al. (1998). | up to 3 years | 
| Duration of Response (Excluding Patient Choice and Non-compliance) | Response [complete response (CR), partial response (PR), and stable disease (SD)] was assessed after approximately 2 months, 6 months and then every 4 months, until progression of disease. Response and progression of disease evaluation is based on the criteria reported by Blade, et al. (1998). | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Have Responded to TBL12 | Response to TBL12 is defined as SD or better after 2 cycles of TBL12. The evaluation of SD, PR, or CR is based on the report by Blade et al. (1998) | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple myeloma, myeloma, asymptomatic myeloma, smoldering myeloma, Asymptomatic (smoldering) myeloma