A Trial of TBL-12 Sea Cucumber Extract in Patients With Untreated Asymptomatic Myeloma

• To estimate the response rate (stable disease or better after 2 cycles) of asymptomatic multiple myeloma patients receiving TBL12. [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
  Assessed after approximately 2 months, 6 months and then every 4 months, until progression of disease.
• To study the possible mechanisms involved in the clinical antitumor effect with determination of inhibition of angiogenesis. [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
  Assessed after approximately 2 months, 6 months and then every 4 months, and at time of progression (or end of treatment,if withdrawn prior to progression).
• To estimate the time to progression of asymptomatic multiple myeloma patients receiving TBL12 [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
  Assessed after approximately 2 months, 6 months and then every 4 months, until progression of disease.

TBL12 (the study drug) will be given orally at a dose of 2 units (of 20 mL each) twice a day, in 4 week cycles, until disease progression or until there is sign of disease progression. Each 'unit' is a liquid gel packaged in a 20 mL container sealed with an aluminum lid. All patients will initially receive 2 cycles of therapy (eight weeks), followed by re-staging with urine and/or serum protein assessments. The patient will continue being treated on study if their disease is stable or responding. All patients will then be re-staged four cycles later (end of cycle 6) with protein studies.

TBL12 has been used by a number of patients as a food supplement without any side effects. This study proposes to determine the clinical activity of this agent in patients with asymptomatic multiple myeloma. It is believed that TBL-12 will help delay the onset of active multiple myeloma, with very few-if any- side effects.

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. We 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.

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