A Phase 1/2 interventional study of BG00002 (natalizumab) in Multiple Myeloma, sponsored by Biogen. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-09-19.
Sponsored by Biogen · Phase 1/2, Interventional, and Treatment
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.
3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.
This study's enrollment of 6 is below the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →Biogen is the lead sponsor of 511 studies on the registry; 24 are open to participants now.
Of its 100 completed or terminated interventional studies of FDA-regulated products, 49 (49%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
Drug: BG00002 (natalizumab)
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
Drug: BG00002 (natalizumab)
Also known as: Tysabri
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.
Time frame: 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).
Time frame: 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.
Time frame: Day 1 up to Month 6
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.
Time frame: 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.
Time frame: 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).
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)
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.
| Milestone | Natalizumab 300 mg | Natalizumab 450 mg |
|---|---|---|
| Started | 3 | 3 |
| Completed | 0 | 0 |
| Not completed | 3 | 3 |
| Withdrew: Disease progression | 2 | 2 |
| Withdrew: No disease response after cycle 6 | 0 | 1 |
| Withdrew: Physician decision | 1 | 0 |
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.
| participants | Natalizumab 300 mg | Natalizumab 450 mg |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | 0 | 0 |
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006).
No measurements were reported for this outcome.
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.
| participants | Natalizumab 300 mg | Natalizumab 450 mg |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | 3 | 3 |
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.
| participants | Natalizumab 300 mg | Natalizumab 450 mg |
|---|---|---|
| Number Of Participants Who Achieve A Complete Response | 0 | 0 |
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.
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over 463 days (from date of first treatment on 4 September 2008 until the Last Patient Last Visit on 10 December 2009).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Natalizumab 300 mg | — | 1/3 (33.3%) | 3/3 (100%) |
| Natalizumab 450 mg | — | 1/3 (33.3%) | 3/3 (100%) |
| Event | Natalizumab 300 mg | Natalizumab 450 mg |
|---|---|---|
| PneumoniaInfections and infestations | 1/3 | 0/3 |
| Acute Renal FailureRenal and urinary disorders | 0/3 | 1/3 |
| Event | Natalizumab 300 mg | Natalizumab 450 mg |
|---|---|---|
| PneumoniaInfections and infestations | 1/3 | 1/3 |
| Respiratory Tract InfectionInfections and infestations | 1/3 | 0/3 |
| AnaemiaBlood and lymphatic system disorders | 1/3 | 0/3 |
| LymphopeniaBlood and lymphatic system disorders | 1/3 | 0/3 |
| NeutropeniaBlood and lymphatic system disorders | 1/3 | 1/3 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/3 | 1/3 |
| DehydrationMetabolism and nutrition disorders | 1/3 | 0/3 |
| HypercalcaemiaMetabolism and nutrition disorders | 1/3 | 0/3 |
| HypokalaemiaMetabolism and nutrition disorders | 1/3 | 0/3 |
| HyponatraemiaMetabolism and nutrition disorders | 1/3 | 0/3 |
| Age, Continuous(years) | Natalizumab 300 mg | Natalizumab 450 mg | Total |
|---|---|---|---|
| Median | 67.0 (57 to 75) | 68.0 (50 to 75) | 67.5 (50 to 75) |
| Sex: Female, Male(Participants) | Natalizumab 300 mg | Natalizumab 450 mg | Total |
|---|---|---|---|
| Female | 2 | 1 | 3 |
| Male | 1 | 2 | 3 |
The record gives a start of Sep 2008, a primary completion of Dec 2009 and a completion of Dec 2009. It does not say whether these dates are actual or estimated.
Results were first posted in Sep 2014, 4 years 9 months after primary completion.
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Studies of the drug tested here: Natalizumab