A Trial of TBL12 Sea Cucumber Extract in Patients With Untreated Asymptomatic Myeloma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sea cucumber extract 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
|
Outcome Measures
Primary Outcome Measures
- Duration of Response (All Treated Patients) [up to 3 years]
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).
- Duration of Response (Excluding Patient Choice and Non-compliance) [up to 3 years]
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).
Secondary Outcome Measures
- Percentage of Patients Who Have Responded to TBL12 [2 months]
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)
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York University School of Medicine, Clinical Cancer Center | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
- Unicorn Pacific Corporation
Investigators
- Principal Investigator: Amitabha Mazumder, MD, NYU School of Medicine, Clinical Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
- NYU# 10-02181
Study Results
Participant Flow
| Recruitment Details | From March 2011 to October 2012, 20 patients were enrolled to the study from Perlmutter Cancer Center at NYU Lagone Medical Center. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sea Cucumber Extract (TBL 12) |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 20 |
| COMPLETED | 15 |
| NOT COMPLETED | 5 |
Baseline Characteristics
| Arm/Group Title | Sea Cucumber Extract (TBL 12) |
|---|---|
| Arm/Group Description | 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. TBL-12 |
| Overall Participants | 20 |
| Age, Customized (participants) [Number] | |
| 35-44 years |
1
5%
|
| 45-53 years |
2
10%
|
| 54-63 years |
9
45%
|
| 64-73 years |
5
25%
|
| 74-83 years |
3
15%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
40%
|
| Male |
12
60%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
10%
|
| White |
15
75%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
3
15%
|
| Region of Enrollment (participants) [Number] | |
| United States |
20
100%
|
Outcome Measures
| Title | Duration of Response (All Treated Patients) |
|---|---|
| Description | 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). |
| Time Frame | up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sea Cucumber Extract (TBL 12) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 20 |
| Median (Full Range) [months] |
19.7
|
| Title | Percentage of Patients Who Have Responded to TBL12 |
|---|---|
| Description | 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) |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| all patients |
| Arm/Group Title | Sea Cucumber Extract (TBL 12) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 20 |
| Number [percentage of participants] |
100
500%
|
| Title | Duration of Response (Excluding Patient Choice and Non-compliance) |
|---|---|
| Description | 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). |
| Time Frame | up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients or the patients excluding personal choice or non-compliance |
| Arm/Group Title | Sea Cucumber Extract (TBL 12) |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 15 |
| Median (Full Range) [months] |
21.0
|
Adverse Events
| Time Frame | up to one year | |
|---|---|---|
| Adverse Event Reporting Description | All adverse events regardless of attribution are reported here. | |
| Arm/Group Title | Sea Cucumber Extract (TBL 12) | |
| Arm/Group Description | 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. | |
All Cause Mortality |
||
| Sea Cucumber Extract (TBL 12) | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Sea Cucumber Extract (TBL 12) | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/20 (15%) | |
| Gastrointestinal disorders | ||
| Nausea | 1/20 (5%) | |
| Infections and infestations | ||
| Infection with Grade 3 or 4 neutrophils: Skin (cellulites) | 1/20 (5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Pain: Chest/thorax NOS | 1/20 (5%) | |
Other (Not Including Serious) Adverse Events |
||
| Sea Cucumber Extract (TBL 12) | ||
| Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin | 3/20 (15%) | |
| Cardiac disorders | ||
| Hypertension | 1/20 (5%) | |
| Left ventricular diastolic dysfunction | 1/20 (5%) | |
| Cardiac General - Other: heart flutter | 1/20 (5%) | |
| Eye disorders | ||
| Vision-blurred vision | 1/20 (5%) | |
| Dry Eyes | 1/20 (5%) | |
| Gastrointestinal disorders | ||
| Distension/bloating, abdominal | 1/20 (5%) | |
| Pain: Abdomen NOS | 1/20 (5%) | |
| Anorexia | 1/20 (5%) | |
| Perforation, GI: Colon | 1/20 (5%) | |
| Constipation | 7/20 (35%) | |
| Diarrhea | 4/20 (20%) | |
| Enteritis (inflammation of the small bowel) | 1/20 (5%) | |
| Flatulence | 1/20 (5%) | |
| Pain: Intestine | 1/20 (5%) | |
| Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation) | 1/20 (5%) | |
| Nausea | 5/20 (25%) | |
| Pain: Stomach | 3/20 (15%) | |
| Mucositis/stomatitis (functional/symptomatic): Oral cavity | 1/20 (5%) | |
| Vomiting | 3/20 (15%) | |
| General disorders | ||
| Fatigue (asthenia, lethargy, malaise) | 8/20 (40%) | |
| Fever (in the absence of neutropenia) | 2/20 (10%) | |
| Rigors/chills | 2/20 (10%) | |
| Weight loss | 1/20 (5%) | |
| Pain NOS | 3/20 (15%) | |
| Edema: limb | 2/20 (10%) | |
| Immune system disorders | ||
| Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) | 1/20 (5%) | |
| Allergic reaction/ hypersensitivity | 5/20 (25%) | |
| Allergy/Immunology, other: autoimmune disorder | 1/20 (5%) | |
| Infections and infestations | ||
| Infection with normal ANC or Grade 1 or 2 neutrophils: Bladder (urinary) | 2/20 (10%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Bronchus | 3/20 (15%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Mucosa | 3/20 (15%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Lung (pneumonia) | 4/20 (20%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Sinus | 2/20 (10%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Urinary tract NOS | 2/20 (10%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Vagina | 1/20 (5%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Upper airway NOS | 10/20 (50%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Stomach | 2/20 (10%) | |
| Infection with normal ANC or Grade 1 or 2 neutrophils: Oral cavity-gums (gingivitis) | 1/20 (5%) | |
| Infection - Other: staph infection (skin) | 1/20 (5%) | |
| Infection with unknown ANC: Sinus | 1/20 (5%) | |
| Infection with unknown ANC: Vagina | 1/20 (5%) | |
| Infection, other: upper respiratory infection | 1/20 (5%) | |
| Infection, other: abdominal infection | 1/20 (5%) | |
| Investigations | ||
| Leukocytes (total WBC) | 2/20 (10%) | |
| Metabolism and nutrition disorders | ||
| Creatinine | 2/20 (10%) | |
| Potassium, serum-high (hyperkalemia) | 1/20 (5%) | |
| Sodium, serum-high (hypernatremia) | 1/20 (5%) | |
| Uric acid, serum-high (hyperuricemia) | 2/20 (10%) | |
| Metabolic/Laboratory - Other: elevated BUN | 1/20 (5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Pain: Joint | 1/20 (5%) | |
| Arthritis (non-septic): | 2/20 (10%) | |
| Pain: Back | 9/20 (45%) | |
| Pain: Bone | 1/20 (5%) | |
| Pain: Chest/thorax NOS | 1/20 (5%) | |
| Fracture | 1/20 (5%) | |
| Extremity-lower (gait/walking) | 1/20 (5%) | |
| Muscle weakness, generalized or specific area (not due to neuropathy): Whole body/generalized | 2/20 (10%) | |
| Pain: Neck | 3/20 (15%) | |
| Pain: Extremity-limb | 14/20 (70%) | |
| Seroma | 1/20 (5%) | |
| Pain: Buttock | 1/20 (5%) | |
| Lumbar spine-range of motion | 1/20 (5%) | |
| Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower | 2/20 (10%) | |
| Pain, other: hip | 1/20 (5%) | |
| Nervous system disorders | ||
| Dizziness | 6/20 (30%) | |
| Pain: Head/headache | 6/20 (30%) | |
| Memory impairment | 1/20 (5%) | |
| Pain: Neuralgia/peripheral nerve | 1/20 (5%) | |
| Neuropathy: motor | 2/20 (10%) | |
| Neuropathy: sensory | 3/20 (15%) | |
| Psychiatric disorders | ||
| Mood alteration: Agitation | 1/20 (5%) | |
| Mood alteration: Anxiety | 1/20 (5%) | |
| Mood alteration: Depression | 2/20 (10%) | |
| Insomnia | 1/20 (5%) | |
| Renal and urinary disorders | ||
| Incontinence, urinary | 1/20 (5%) | |
| Urinary retention (including neurogenic bladder): | 1/20 (5%) | |
| Reproductive system and breast disorders | ||
| Pain: Pelvis | 1/20 (5%) | |
| Vaginal discharge (non-infectious) | 1/20 (5%) | |
| Erectile Dysfunction | 1/20 (5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 4/20 (20%) | |
| Dyspnea (shortness of breath) | 1/20 (5%) | |
| Flu-like syndrome | 2/20 (10%) | |
| Edema, larynx | 1/20 (5%) | |
| Pain: Throat/pharynx/larynx | 3/20 (15%) | |
| Nasal Cavity/Paranasal Sinus Reactions | 1/20 (5%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash: acne/acneiform: | 3/20 (15%) | |
| Rash/desquamation | 1/20 (5%) | |
| Dry skin | 2/20 (10%) | |
| Photosensitivity | 1/20 (5%) | |
| Pruritus/itching | 3/20 (15%) | |
| Dermatology/skin, other: finger splinter | 1/20 (5%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Amitabha Mazumder, MD |
|---|---|
| Organization | Perlmutter Cancer Center at NYU Langone |
| Phone | 212-731-5757 |
| amitabha.mazumder@nyumc.org |
- NYU# 10-02181