Back to resultsA Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
5.0g SRT501
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Subject must be male or female ≥ 18 years at the time of signing Informed Consent.
- Subject was previously diagnosed with Multiple Myeloma and has failed at least one prior treatment regimen for the disease.
- Subject must have measurable disease.
- Subjects must have relapsed or relapsed/refractory disease as defined in Appendix 4.
- Subject must have a life expectancy of greater than 6 months.
- Subject has an ECOG Performance status of 0 to 2 (Appendix 2).
- Subject has no prior history of HIV-1, HIV-2, Hepatitis B or C infection.
- Subject has a normal 12 lead ECG or an ECG with an abnormality considered to be clinically insignificant.
- Subject has the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
- Subject must be able to adhere to the study visit schedule and other protocol requirements.
- Subject must understand and voluntarily sign an informed consent document.
- All subjects of reproductive potential must agree prior to study entry to use adequate contraception (hormonal or double barrier method of birth control; abstinence) for the duration of the study dosing and at least 12 weeks after completion of study drug.
Adequate end organ function, defined as the following:
- Total bilirubin < 2 x ULN, unless attributable to Gilbert's disease
- ALT (SGPT) and AST (SGOT) < 2.5 x ULN
- Creatinine < 2.0 x ULN
- ANC > 0.5 x 10^9/L
- Platelets > 20,000 cells/mm3
Exclusion Criteria:
- Intolerance to resveratrol, SRT501 or bortezomib or significant allergy to either compound, boron or mannitol or significant prior toxicity with either agent that would preclude the safe use of that agent. Prior therapy with either compound is permitted.
- Subjects with other active malignancy, with the exception of basal cell or squamous cell carcinoma of the skin.
- An uncontrolled intercurrent illness including, but not limited to, recent (≤ 6 months), ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, acute diffuse infiltrative pulmonary or pericardial disease, or psychiatric illness/social situations that would limit compliance with study requirements.
- Subject with a history of or current gastro-intestinal diseases influencing drug absorption, with the exception of an appendectomy.
- Women who are breast-feeding, pregnant, expect to become pregnant during the course of the study, or are sexually active in a heterosexual relationship and are not using a medically acceptable double barrier method birth control. Confirmation that the subject is not pregnant must be established by a negative serum beta-hCG pregnancy test result obtained during the Screening period. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Women relying solely on oral contraceptives for birth control are excluded.
- Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to signing Informed Consent or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Subjects who are on any concurrent medications that may exhibit anti-neoplastic therapy, with the exception of < 10 mg of prednisone or equivalent as indicated for other medical conditions, or up to 100 mg of hydrocortisone as premedication for administration of certain medications or blood products.
- Subjects currently taking any investigational therapies and/or dietary supplements containing resveratrol.
- Subjects with peripheral neuropathy of Grade 2 or greater.
- Subjects with uncontrolled bleeding.
- Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 20,000 cells/mm3).
- Subjects with a hemoglobin < 8.0 g/dL. Transfusions and/or EPO treatment are permitted in subjects who are potentially excluded by this criteria.
- Any condition, including laboratory abnormalities, that in the opinion of the Investigator, would preclude treatment.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
5.0 g SRT501 will be administered for 20 consecutive days in a 21 day cycle for a maximum of 12 cycles. SRT501 will be administered at the same time each morning (approximately 15-30 minutes after breakfast) on all dosing days. No SRT501 administration will occur on Day 21 of each cycle. After the first two cycles of SRT501, any subject who exhibits stable disease or better with SRT501 monotherapy (5.0 g/day) will continue for an additional two cycles. If, after the first two cycles, a subject exhibits PD, that subject will receive bortezomib (1.3 mg/m2 on Day 1, Day 4, Day 8, and Day 11 in a 21 day cycle) in conjunction with SRT501. Bortezomib will be administered prior to breakfast and SRT501 administration. If after two additional cycles of SRT501 monotherapy (4 cycles total), the subject exhibits a MR or better, they they will remain on SRT501 therapy. If PD or SD are exibited, they are to undergo bortezomib regiment listed above.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Number of Participants With Overall Response Rate
Overall response rate, defines proportion of participants with Complete response (CR), Partial response (PR) or Minimal response (MR) as best response for all cycles. In atleast 2 determinations for minimum of 6 week (Wks) for every criteria listed. CR defined as disappearance of original monoclonal (MC) paraprotein (PP) in blood and urine on immunofixation determinations (IFD); < 5 % plasma cells in bone marrow; no increase in size or number of lytic bone lesions (LBLs); disappearance of soft tissue plasmacytomas (STP). PR defined as >= 50% reduction (RE) in level of serum MC PP for 2 IFDs; if present RE in 24 hour urinary light chain excretion (ULCE) by >= 90% RE or <200 mg; >= 50% RE in STP for; no increase in size or number of LBLs. MR criteria defined were >= 25% to <=49% RE serum MC PP; if present 50 to 89% RE in 24 hour LCE exceeding 200 mg/24 hour; 25% to 49% RE in size of STP; no increase in size or number of LBLs.
Number of Participants With Partial Response (PR) as Best Response (BR)
PR includes some, but not all, criteria for CR providing the remaining criteria are satisfied: ≥50% reduction in the level of serum monoclonal paraprotein for at least 2 immunofixation determinations for a minimum of 6 weeks, If present, reduction in 24 hr urinary light chain excretion by either ≥90% or to <200 mg for at least 2 determinations for a minimum of 6 weeks, ≥50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for a minimum of 6 weeks, No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
Number of Participants With Minor Response (MR) as Best Response (BR)
MR includes some, but not all, criteria for PR providing the remaining criteria satisfied: ≥25% to ≤ 49% reduction in the level of serum monoclonal paraprotein for at least 2 immunofixation determinations for a minimum of 6 weeks, If present, a 50 to 89% reduction in 24 hr light chain excretion, which still exceeds 200 mg/24 hr, for at least 2 determinations for a minimum of 6 weeks, 25-49% reduction in the size of plasmacytomas (by clinical or radiographic examination) for a minimum of 6 weeks, No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
Number of Participants With Partial Response (PR) as Last Observed Response (LOR)
PR includes some, but not all, criteria for CR providing the remaining criteria are satisfied: ≥50% reduction in the level of serum monoclonal paraprotein for at least 2 immunofixation determinations for a minimum of 6 weeks, If present, reduction in 24 hr urinary light chain excretion by either ≥90% or to <200 mg for at least 2 determinations for a minimum of 6 weeks, ≥50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for a minimum of 6 weeks, No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
Number of Participants With Stable Disease (SD) as Best Response (BR)
Stable disease included not meeting the criteria for MR or PD.
Number of Participants With Stable Disease (SD) as Last Observed Response (LOR)
Stable disease included not meeting the criteria for MR or PD.
Number of Participants With Progressive Disease (PD) PD as Best Response (BR)
PD includes one or more of the following criteria: >25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, >25% increase in 24 hr urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 hr and confirmed on a repeat investigation, >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%., Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas, Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture), Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Number of Participants With Progressive Disease (PD) PD as Last Observed Response (LOR)
PD includes one or more of the following criteria: >25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, >25% increase in 24 hr urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 hr and confirmed on a repeat investigation, >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%., Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas, Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture), Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Time to Disease Progression
Time to disease progression was defined as the time from first dose until objective tumor progression. Participants who did not experience tumor progression were censored at their last known date in the study. It was estimated using Kaplan-Meier methodology. Participants who did not experience tumor progression were censored at their last known date in the study. The first quartile for time to disease progression was evaluated when 25th percentile of participants of mITT population reported disease progression. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 75th percentile of participants reported disease progression at the end of the study period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA).
Change From Baseline in Hematology: White Blood Cell (WBC) Count, Neutrophils, Lymphocytes, Platelets
Blood samples collected to evaluate the hematology parameters were WBC count, neutrophils, lymphocytes and platelets. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Change From Baseline in Hematology: Hematocrit
Blood samples were collected to evaluate the hematology parameter hematocrit. Change from Baseline was defined as the value of baseline minus from the End of study visit. Baseline was defined as Day 1.
Change From Baseline in Hematology: Hemoglobin
Blood samples were collected to evaluate the hematology parameter hemoglobin. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Change From Baseline in Hematology: Red Blood Cell (RBC)
Blood samples were collected to evaluate the hematology parameter RBC. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Change From in Baseline Biochemistry: Serum Creatinine, Total Bilirubin
Blood samples were collected to evaluate hematology parameters serum creatinine and total bilirubin. Change from Baseline was defined as the value of baseline minus from the End of study visit. Baseline was defined as Day 1.
Change From Baseline in Biochemistry -Urea, Bicarbonate
Blood samples were collected to evaluate the biochemistry parameter urea and bicarbonate. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Change From Baseline in Biochemistry: Prothrombin Time (PT)/ International Normalized Ratio (INR)
Blood samples were collected to evaluate the biochemistry parameter PT/INR. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Secondary Outcome Measures
Plasma Concentrations of SRT501 at Indicated Time Points
Pharmacokinetic sampling on Day1/2 and Day 20/21 of Cycle 1 for participants ready to participate was planned. The sampling was planned to be collected at timepoints on Cycle 1 Day 1 at pre-dose, 30 minute, 1 hour, 2 hour, 4 hour, 6 hour and 24 hour post-dose and the same timepoints on Day 2 and Day 20 post- dose. It was to be collected in participants who fasted atleast for an hour. Due to early termination of the study, the data for Pharmacokinetic analysis was not collected.
Full Information
NCT ID
NCT00920556
First Posted
June 12, 2009
Last Updated
October 17, 2018
Sponsor
Sirtris, a GSK Company
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT00920556
Brief Title
A Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple Myeloma
Official Title
A Phase II, Open-Label, Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Study terminated.24 subjects enrolled;provided adequate data for decision making.
Study Start Date
March 30, 2009 (Actual)
Primary Completion Date
November 4, 2010 (Actual)
Study Completion Date
November 4, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sirtris, a GSK Company
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary purpose of this study is to determine the safety and tolerability of SRT501 (5.0 g) with or without concurrent bortezomib administration, when administered once daily in 21 day cycles, in male and female subjects with Multiple Myeloma.
The purpose is also to define objective response (ORR, CR, PR, MR, SD) and time to progression (TTP) of SRT501 with or without concurrent bortezomib administered concurrently in male and female subjects with Multiple Myeloma.
In addition, 15 subjects will participate in a sub-study to assess the pharmacokinetics of SRT501.
Detailed Description
This is an, open-label, phase II study of SRT501, alone or in combination with bortezomib, in subjects with measurable Multiple Myeloma. Sixty-one (61) evaluable subjects, who fulfill the inclusion/exclusion criteria, will be enrolled in this study. Pharmacokinetic (PK) samples will be collected from a subset of 15 subjects to determine SRT501 plasma concentrations in this patient population. Subjects will sign the informed consent form prior to any study related procedures. If eligible, subjects will receive 5.0 g of SRT501 to be administered for 20 consecutive days in a 21 day cycle for a maximum of 12 cycles. SRT501 will be administered as an oral suspension product at the same time each morning (approximately 15-30 minutes following consumption of breakfast) on all dosing days. Safety assessments will be performed continuously throughout the cycle and these will be reviewed for all subjects at Day 21 of each cycle prior to subjects proceeding to the next cycle. SRT501 will not be administered on Day 21 of each cycle. Subjects will be assessed for efficacy and response of SRT501 at the end of every 2 cycles (6 weeks) of treatment. When necessary, a bone marrow biopsy and CT (or appropriate radiographic imaging) of the chest and abdomen/pelvis will be performed to confirm response. After the first two cycles of SRT501 treatment and review of the efficacy and response analysis, any subject who exhibits stable disease or better with SRT501 monotherapy may continue on SRT501 monotherapy (5.0 g/day) for an additional two cycles. If, after the first two cycles of SRT501 monotherapy, a subject exhibits PD, then that subject will receive bortezomib (1.3 mg/ m2 on Day 1, Day 4, Day 8, and Day 11 in a 21 day cycle) in conjunction with SRT501 (5.0 g/day). Bortezomib will be administered prior to SRT501 administration. If after two additional cycles of SRT501 monotherapy (4 cycles total), the subject exhibits a MR or better, they will remain on SRT501 (5.0 g/day) treatment until they are judged to have SD or PD. At the time the subject is judged to have SD or PD after receiving at least four cycles of SRT501 (5.0 g/day) monotherapy, then they may also receive bortezomib (1.3 mg/m2 on Day 1, Day 4, Day 8, and Day 11 in a 21 day cycle) in conjunction with daily SRT501 dosing. If at any point while a subject is receiving SRT501 and bortezomib the subject is assessed to have PD, then they will be removed from the study and will be required to undergo End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
5.0 g SRT501 will be administered for 20 consecutive days in a 21 day cycle for a maximum of 12 cycles. SRT501 will be administered at the same time each morning (approximately 15-30 minutes after breakfast) on all dosing days. No SRT501 administration will occur on Day 21 of each cycle.
After the first two cycles of SRT501, any subject who exhibits stable disease or better with SRT501 monotherapy (5.0 g/day) will continue for an additional two cycles. If, after the first two cycles, a subject exhibits PD, that subject will receive bortezomib (1.3 mg/m2 on Day 1, Day 4, Day 8, and Day 11 in a 21 day cycle) in conjunction with SRT501. Bortezomib will be administered prior to breakfast and SRT501 administration.
If after two additional cycles of SRT501 monotherapy (4 cycles total), the subject exhibits a MR or better, they they will remain on SRT501 therapy. If PD or SD are exibited, they are to undergo bortezomib regiment listed above.
Intervention Type
Drug
Intervention Name(s)
5.0g SRT501
Intervention Description
5.0g SRT501 will be supplied in clinical kits as a powder which will be reconstituted with vehicle and water into a liquid suspension. SRT501 will be administered orally as a liquid suspension for 20 consecutive days in each 21 day cycle.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
Bortezomib (1.3 mg/m2) will be given as an intravenous solution in a 3-5 second push on Day 1, 4, 8 and 11 in every 21 day cycle.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time Frame
Approximately up to 12 cycles of 3 weeks each
Title
Number of Participants With Overall Response Rate
Description
Overall response rate, defines proportion of participants with Complete response (CR), Partial response (PR) or Minimal response (MR) as best response for all cycles. In atleast 2 determinations for minimum of 6 week (Wks) for every criteria listed. CR defined as disappearance of original monoclonal (MC) paraprotein (PP) in blood and urine on immunofixation determinations (IFD); < 5 % plasma cells in bone marrow; no increase in size or number of lytic bone lesions (LBLs); disappearance of soft tissue plasmacytomas (STP). PR defined as >= 50% reduction (RE) in level of serum MC PP for 2 IFDs; if present RE in 24 hour urinary light chain excretion (ULCE) by >= 90% RE or <200 mg; >= 50% RE in STP for; no increase in size or number of LBLs. MR criteria defined were >= 25% to <=49% RE serum MC PP; if present 50 to 89% RE in 24 hour LCE exceeding 200 mg/24 hour; 25% to 49% RE in size of STP; no increase in size or number of LBLs.
Time Frame
Approximately up to 12 cycles of 3 weeks
Title
Number of Participants With Partial Response (PR) as Best Response (BR)
Description
PR includes some, but not all, criteria for CR providing the remaining criteria are satisfied: ≥50% reduction in the level of serum monoclonal paraprotein for at least 2 immunofixation determinations for a minimum of 6 weeks, If present, reduction in 24 hr urinary light chain excretion by either ≥90% or to <200 mg for at least 2 determinations for a minimum of 6 weeks, ≥50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for a minimum of 6 weeks, No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
Time Frame
Up to 12 cycles of 3 weeks each
Title
Number of Participants With Minor Response (MR) as Best Response (BR)
Description
MR includes some, but not all, criteria for PR providing the remaining criteria satisfied: ≥25% to ≤ 49% reduction in the level of serum monoclonal paraprotein for at least 2 immunofixation determinations for a minimum of 6 weeks, If present, a 50 to 89% reduction in 24 hr light chain excretion, which still exceeds 200 mg/24 hr, for at least 2 determinations for a minimum of 6 weeks, 25-49% reduction in the size of plasmacytomas (by clinical or radiographic examination) for a minimum of 6 weeks, No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
Time Frame
Up to 12 cycles of 3 weeks each
Title
Number of Participants With Partial Response (PR) as Last Observed Response (LOR)
Description
PR includes some, but not all, criteria for CR providing the remaining criteria are satisfied: ≥50% reduction in the level of serum monoclonal paraprotein for at least 2 immunofixation determinations for a minimum of 6 weeks, If present, reduction in 24 hr urinary light chain excretion by either ≥90% or to <200 mg for at least 2 determinations for a minimum of 6 weeks, ≥50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for a minimum of 6 weeks, No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
Time Frame
Up to 12 cycles of 3 weeks each
Title
Number of Participants With Stable Disease (SD) as Best Response (BR)
Description
Stable disease included not meeting the criteria for MR or PD.
Time Frame
Up to 12 cycles of 3 weeks each
Title
Number of Participants With Stable Disease (SD) as Last Observed Response (LOR)
Description
Stable disease included not meeting the criteria for MR or PD.
Time Frame
Up to 12 cycles of 3 weeks each
Title
Number of Participants With Progressive Disease (PD) PD as Best Response (BR)
Description
PD includes one or more of the following criteria: >25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, >25% increase in 24 hr urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 hr and confirmed on a repeat investigation, >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%., Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas, Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture), Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Time Frame
Up to 12 cycles of 3 weeks each
Title
Number of Participants With Progressive Disease (PD) PD as Last Observed Response (LOR)
Description
PD includes one or more of the following criteria: >25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, >25% increase in 24 hr urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 hr and confirmed on a repeat investigation, >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%., Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas, Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture), Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).
Time Frame
Up to 12 cycles of 3 weeks each
Title
Time to Disease Progression
Description
Time to disease progression was defined as the time from first dose until objective tumor progression. Participants who did not experience tumor progression were censored at their last known date in the study. It was estimated using Kaplan-Meier methodology. Participants who did not experience tumor progression were censored at their last known date in the study. The first quartile for time to disease progression was evaluated when 25th percentile of participants of mITT population reported disease progression. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 75th percentile of participants reported disease progression at the end of the study period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA).
Time Frame
From Day 1 till disease progression (approximately 12 cycles of 3 weeks each)
Title
Change From Baseline in Hematology: White Blood Cell (WBC) Count, Neutrophils, Lymphocytes, Platelets
Description
Blood samples collected to evaluate the hematology parameters were WBC count, neutrophils, lymphocytes and platelets. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Title
Change From Baseline in Hematology: Hematocrit
Description
Blood samples were collected to evaluate the hematology parameter hematocrit. Change from Baseline was defined as the value of baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Title
Change From Baseline in Hematology: Hemoglobin
Description
Blood samples were collected to evaluate the hematology parameter hemoglobin. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Title
Change From Baseline in Hematology: Red Blood Cell (RBC)
Description
Blood samples were collected to evaluate the hematology parameter RBC. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Title
Change From in Baseline Biochemistry: Serum Creatinine, Total Bilirubin
Description
Blood samples were collected to evaluate hematology parameters serum creatinine and total bilirubin. Change from Baseline was defined as the value of baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Title
Change From Baseline in Biochemistry -Urea, Bicarbonate
Description
Blood samples were collected to evaluate the biochemistry parameter urea and bicarbonate. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Title
Change From Baseline in Biochemistry: Prothrombin Time (PT)/ International Normalized Ratio (INR)
Description
Blood samples were collected to evaluate the biochemistry parameter PT/INR. Change from Baseline was defined as the value of Baseline minus from the End of study visit. Baseline was defined as Day 1.
Time Frame
Baseline (Day 1) and End of Study assessments/follow-up approximately 28 days (+/- 7 days) following the last dose of SRT501 or SRT501 and bortezomib (approximately 280 days)
Secondary Outcome Measure Information:
Title
Plasma Concentrations of SRT501 at Indicated Time Points
Description
Pharmacokinetic sampling on Day1/2 and Day 20/21 of Cycle 1 for participants ready to participate was planned. The sampling was planned to be collected at timepoints on Cycle 1 Day 1 at pre-dose, 30 minute, 1 hour, 2 hour, 4 hour, 6 hour and 24 hour post-dose and the same timepoints on Day 2 and Day 20 post- dose. It was to be collected in participants who fasted atleast for an hour. Due to early termination of the study, the data for Pharmacokinetic analysis was not collected.
Time Frame
Cycle 1 Day 1, Cycle 1 Day 2 and Cycle 1 Day 20 at pre-dose, 30 minute, 1 hour, 2 hour, 4 hour, 6 hour and 24 hour post-dose. Day 2 and Day 20, samples collected post-dose. Each cycle duration was 21 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject must be male or female ≥ 18 years at the time of signing Informed Consent.
Subject was previously diagnosed with Multiple Myeloma and has failed at least one prior treatment regimen for the disease.
Subject must have measurable disease.
Subjects must have relapsed or relapsed/refractory disease as defined in Appendix 4.
Subject must have a life expectancy of greater than 6 months.
Subject has an ECOG Performance status of 0 to 2 (Appendix 2).
Subject has no prior history of HIV-1, HIV-2, Hepatitis B or C infection.
Subject has a normal 12 lead ECG or an ECG with an abnormality considered to be clinically insignificant.
Subject has the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
Subject must be able to adhere to the study visit schedule and other protocol requirements.
Subject must understand and voluntarily sign an informed consent document.
All subjects of reproductive potential must agree prior to study entry to use adequate contraception (hormonal or double barrier method of birth control; abstinence) for the duration of the study dosing and at least 12 weeks after completion of study drug.
Adequate end organ function, defined as the following:
Total bilirubin < 2 x ULN, unless attributable to Gilbert's disease
ALT (SGPT) and AST (SGOT) < 2.5 x ULN
Creatinine < 2.0 x ULN
ANC > 0.5 x 10^9/L
Platelets > 20,000 cells/mm3
Exclusion Criteria:
Intolerance to resveratrol, SRT501 or bortezomib or significant allergy to either compound, boron or mannitol or significant prior toxicity with either agent that would preclude the safe use of that agent. Prior therapy with either compound is permitted.
Subjects with other active malignancy, with the exception of basal cell or squamous cell carcinoma of the skin.
An uncontrolled intercurrent illness including, but not limited to, recent (≤ 6 months), ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, acute diffuse infiltrative pulmonary or pericardial disease, or psychiatric illness/social situations that would limit compliance with study requirements.
Subject with a history of or current gastro-intestinal diseases influencing drug absorption, with the exception of an appendectomy.
Women who are breast-feeding, pregnant, expect to become pregnant during the course of the study, or are sexually active in a heterosexual relationship and are not using a medically acceptable double barrier method birth control. Confirmation that the subject is not pregnant must be established by a negative serum beta-hCG pregnancy test result obtained during the Screening period. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Women relying solely on oral contraceptives for birth control are excluded.
Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to signing Informed Consent or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Subjects who are on any concurrent medications that may exhibit anti-neoplastic therapy, with the exception of < 10 mg of prednisone or equivalent as indicated for other medical conditions, or up to 100 mg of hydrocortisone as premedication for administration of certain medications or blood products.
Subjects currently taking any investigational therapies and/or dietary supplements containing resveratrol.
Subjects with peripheral neuropathy of Grade 2 or greater.
Subjects with uncontrolled bleeding.
Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 20,000 cells/mm3).
Subjects with a hemoglobin < 8.0 g/dL. Transfusions and/or EPO treatment are permitted in subjects who are potentially excluded by this criteria.
Any condition, including laboratory abnormalities, that in the opinion of the Investigator, would preclude treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Vejle
ZIP/Postal Code
7100
Country
Denmark
Facility Name
GSK Investigational Site
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5NG
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
23205612
Citation
Popat R, Plesner T, Davies F, Cook G, Cook M, Elliott P, Jacobson E, Gumbleton T, Oakervee H, Cavenagh J. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol. 2013 Mar;160(5):714-7. doi: 10.1111/bjh.12154. Epub 2012 Dec 4. No abstract available.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113222
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113222
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113222
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113222
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113222
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
113222
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
A Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple Myeloma
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