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Sponsor decision due to low enrollment and not safety concerns.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Natalizumab 300 mg | Experimental | Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months. |
|
| Natalizumab 450 mg | Experimental | Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BG00002 (natalizumab) | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 up to Day 28 |
| Objective Response Rate (ORR) | Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). | Day 1 up to Month 6 |
| 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. | Day 1 up to Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Center | Scottsdale | Arizona | United States | |||
| Research Center |
This record includes data up to and including the last data values collected during long-term follow-up (27 January 2010).
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| ID | Title | Description |
|---|---|---|
| FG000 | Natalizumab 300 mg | Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months. |
| FG001 | Natalizumab 450 mg | Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Natalizumab 300 mg | Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months. |
| BG001 | Natalizumab 450 mg | Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | participants | Day 1 up to Day 28 |
|
463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Natalizumab 300 mg | Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biogen Idec Study Medical Director | Biogen Idec | clinicaltrials@biogenidec.com |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D000069442 | Natalizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Day 1 up to Month 6 |
| 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. | Day 1 up to Month 6 |
| 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). | 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) |
| Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) | 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. |
| Rochester |
| Minnesota |
| United States |
| Physician Decision |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. |
|
|
| Primary | Objective Response Rate (ORR) | Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006). | ORR was not calculated because the study was terminated early. | Posted | Day 1 up to Month 6 |
|
|
| Primary | 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. | Posted | Number | participants | Day 1 up to Month 6 |
|
|
|
| Secondary | 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. | Posted | Number | participants | Day 1 up to Month 6 |
|
|
|
| Secondary | 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. | Duration of response was not calculated because the study was terminated early. | Posted | Day 1 up to Month 6 |
|
|
| Secondary | 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). | PK analysis was not performed because the study was terminated early. | Posted | 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) |
|
|
| Secondary | Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) | Analysis of binding saturation of α4 integrin sites was not performed because the study was terminated early. | Posted | 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. |
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Natalizumab 450 mg | Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. | 1 | 3 | 3 | 3 |
| Acute Renal Failure | Renal and urinary disorders | MedDRA 12.1 | Systematic Assessment |
|
| Respiratory Tract Infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Confusional State | Psychiatric disorders | MedDRA 12.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| Blood Creatinine Increased | Investigations | MedDRA 12.1 | Systematic Assessment |
|
| Staphylococcal Infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| Neuropathy Peripheral | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| Renal Failure Acute | Renal and urinary disorders | MedDRA 12.1 | Systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | MedDRA 12.1 | Systematic Assessment |
|
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |