Back to resultsStudy of Natalizumab in Relapsed/Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BG00002 (natalizumab)
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Relapsed or refractory Multiple Myeloma
Eligibility Criteria
Key Inclusion Criteria:
- Relapsed or refractory multiple myeloma that was treated with or was considered inappropriate for treatment with bortezomib and an IMiD® drug (including an analogue).
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
- Corrected calcium <10.6 mg/dL.
Key Exclusion Criteria:
- Candidates for stem cell transplantation willing to undergo transplantation. (Subjects who are candidates for stem cell transplantation, but are not willing to undergo transplant will be eligible for the study.)
- Autologous stem cell transplantation <3 months post-transplant.
- Prior allogeneic stem cell transplantation.
- Nonsecretory myeloma.
- Plasma cell leukemia (>2000/µL circulating plasma cells by standard cell counting differential), hyperleukocytosis (white blood cells >100,000/µL), clinical evidence of hyperviscosity syndrome, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), or primary systemic amyloidosis.
- Subjects who cannot undergo a brain magnetic resonance imaging (MRI) study.
- Clinically significant (as determined by the Investigator) 12 lead electrocardiogram (ECG) abnormalities, including QTc prolongation (>450 ms in males, >470 ms in females).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Research Center
- Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Natalizumab 300 mg
Natalizumab 450 mg
Arm Description
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Outcomes
Primary Outcome Measures
Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs = any ≥grade 3 toxicity related to treatment; treatment delays of ≥7 days due to any toxicity related to treatment, with the exception of hepatic transaminases; or alanine and/or aspartate aminotransferase (ALT and/or AST) >3*upper limit of normal (ULN) with either a total bilirubin >2*ULN or an international normalized ratio (INR) >1.5 related to treatment, or with the appearance of worsening fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia.
Objective Response Rate (ORR)
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006).
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered medicinal (investigational) product and that does not necessarily have a causal relationship with this product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. See the adverse events section of the record for more details.
Secondary Outcome Measures
Number Of Participants Who Achieve A Complete Response
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). Complete Response (CR): negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas , and ≤ 5% plasma cells in the bone marrow. Stringent CR (sCR): CR as defined above, and normal free light chain (FLC) ratio, and absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence, based on a κ/λ ratio of > 4:1 or < 1:2 performed on a minimum of 100 plasma cells.
Kaplan-Meier Estimates for Duration Of Response For Participants With A Response
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). Kaplan-Meier methods were used to estimate the median duration of response and associated 95% confidence intervals.
Pharmacokinetic (PK) Profile Of Natalizumab
PK modeling, either compartmental or noncompartmental-based, was used to describe serum concentrations. Standard PK parameters estimated include: area-under-the-concentration-time curve (AUC), maximum-observed concentration (Cmax), time-to-reach maximum concentration (Tmax), total body clearance (Cl), volume of distribution (Vd), and elimination half-life (t1/2).
Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00675428
Brief Title
Study of Natalizumab in Relapsed/Refractory Multiple Myeloma
Official Title
A Phase 1/2, Two-Arm, Dose-Finding Study of Natalizumab for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision due to low enrollment and not safety concerns.
Study Start Date
September 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objectives of the study are to evaluate the safety profile and the anti-tumor activity of 2 dose levels of natalizumab in participants with relapsed or refractory multiple myeloma. Secondary objectives are to assess the pharmacokinetic (PK) profile of natalizumab in this study population and to assess peripheral blood mononuclear cell (PBMC) saturation of very late antigen-4 (VLA-4, an α4-integrin) and evaluate possible correlations with clinical activity.
Detailed Description
Despite no protocol-defined study stopping criteria being met, the sponsor decided to terminate enrollment after the phase 1 portion was complete and to not move into the phase 2 portion of the study. This decision was made due to difficulty enrolling participants and was not due to any safety concerns.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Relapsed or refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Natalizumab 300 mg
Arm Type
Experimental
Arm Description
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Arm Title
Natalizumab 450 mg
Arm Type
Experimental
Arm Description
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Intervention Type
Drug
Intervention Name(s)
BG00002 (natalizumab)
Other Intervention Name(s)
Tysabri
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs)
Description
DLTs = any ≥grade 3 toxicity related to treatment; treatment delays of ≥7 days due to any toxicity related to treatment, with the exception of hepatic transaminases; or alanine and/or aspartate aminotransferase (ALT and/or AST) >3*upper limit of normal (ULN) with either a total bilirubin >2*ULN or an international normalized ratio (INR) >1.5 related to treatment, or with the appearance of worsening fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia.
Time Frame
Day 1 up to Day 28
Title
Objective Response Rate (ORR)
Description
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006).
Time Frame
Day 1 up to Month 6
Title
Number of Participants With Adverse Events (AEs)
Description
An AE was defined as any untoward medical occurrence in a participant administered medicinal (investigational) product and that does not necessarily have a causal relationship with this product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. See the adverse events section of the record for more details.
Time Frame
Day 1 up to Month 6
Secondary Outcome Measure Information:
Title
Number Of Participants Who Achieve A Complete Response
Description
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). Complete Response (CR): negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas , and ≤ 5% plasma cells in the bone marrow. Stringent CR (sCR): CR as defined above, and normal free light chain (FLC) ratio, and absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence, based on a κ/λ ratio of > 4:1 or < 1:2 performed on a minimum of 100 plasma cells.
Time Frame
Day 1 up to Month 6
Title
Kaplan-Meier Estimates for Duration Of Response For Participants With A Response
Description
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). Kaplan-Meier methods were used to estimate the median duration of response and associated 95% confidence intervals.
Time Frame
Day 1 up to Month 6
Title
Pharmacokinetic (PK) Profile Of Natalizumab
Description
PK modeling, either compartmental or noncompartmental-based, was used to describe serum concentrations. Standard PK parameters estimated include: area-under-the-concentration-time curve (AUC), maximum-observed concentration (Cmax), time-to-reach maximum concentration (Tmax), total body clearance (Cl), volume of distribution (Vd), and elimination half-life (t1/2).
Time Frame
Cycles 1 and 6: Day 1 (before infusion and 0.25, 2, 6 and 24 hours after infusion), Days 8, 15, 22. Cycles 2-5: Day 1 (before infusion and 0.25 hour after infusion)
Title
Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)
Time Frame
Cycle 1: Day 1 (1 hour before infusion and 1 and 24 hours after infusion), Days 8, 15, 22. Cycles 2-5: 1 hour before and 1 hour after infusion). Cycle 6: Day 1 (1 hour before infusion and 1 hour after infusion), Days 8, 15, 22.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Relapsed or refractory multiple myeloma that was treated with or was considered inappropriate for treatment with bortezomib and an IMiD® drug (including an analogue).
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
Corrected calcium <10.6 mg/dL.
Key Exclusion Criteria:
Candidates for stem cell transplantation willing to undergo transplantation. (Subjects who are candidates for stem cell transplantation, but are not willing to undergo transplant will be eligible for the study.)
Autologous stem cell transplantation <3 months post-transplant.
Prior allogeneic stem cell transplantation.
Nonsecretory myeloma.
Plasma cell leukemia (>2000/µL circulating plasma cells by standard cell counting differential), hyperleukocytosis (white blood cells >100,000/µL), clinical evidence of hyperviscosity syndrome, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), or primary systemic amyloidosis.
Subjects who cannot undergo a brain magnetic resonance imaging (MRI) study.
Clinically significant (as determined by the Investigator) 12 lead electrocardiogram (ECG) abnormalities, including QTc prolongation (>450 ms in males, >470 ms in females).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Center
City
Scottsdale
State/Province
Arizona
Country
United States
Facility Name
Research Center
City
Rochester
State/Province
Minnesota
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Natalizumab in Relapsed/Refractory Multiple Myeloma
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