Multiple MyelomaPhase 1/2NCT00675428
Study of Natalizumab in Relapsed/Refractory Multiple Myeloma
A Phase 1/2 study testing BG00002 (natalizumab) in people with Multiple Myeloma, run by Biogen at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- BG00002 (natalizumab)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2008to Dec 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Research Center
Rochester, Minnesota
Research Center
Scottsdale, Arizona
About this study
Official title: A Phase 1/2, Two-Arm, Dose-Finding Study of Natalizumab for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- BG00002 (natalizumab)
- Keywords
- Relapsed or refractory Multiple Myeloma
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BG00002 (natalizumab)Drug
Also called Tysabri
| Study group | Role | What they receive |
|---|---|---|
| Natalizumab 300 mg | Experimental | Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months. Receives: Drug: BG00002 (natalizumab) |
| Natalizumab 450 mg | Experimental | Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. Receives: Drug: BG00002 (natalizumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: Day 1 up to Month 6
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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).
Measured: 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)
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2009
- Study completionDec 2009
Why it stopped: Sponsor decision due to low enrollment and not safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00675428
- Sponsor's protocol ID
- 101MY201
- Status last verified
- Sep 2014
- First submitted
- 6 May 2008
- Last updated
- 19 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Two-Arm, Dose-Finding Study of Natalizumab for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00675428
- Acronym / sponsor ID
- 101MY201
- Conditions
- Multiple Myeloma
- Keywords
- Relapsed or refractory Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision due to low enrollment and not safety concerns.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- Sep 2008
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 9 May 2008 (estimated)
- Results
- Posted 19 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Natalizumab 300 mg | Experimental | Drug: BG00002 (natalizumab)Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months. |
| Natalizumab 450 mg | Experimental | Drug: BG00002 (natalizumab)Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BG00002 (natalizumab)Also: Tysabri | Drug | Natalizumab 300 mg, Natalizumab 450 mg |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Day 1 up to Day 28
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)
Time frame: Day 1 up to Month 6
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)
Time frame: Day 1 up to Month 6
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.
4 secondary outcomes
Number Of Participants Who Achieve A Complete Response
Time frame: Day 1 up to Month 6
Kaplan-Meier Estimates for Duration Of Response For Participants With A Response
Time frame: Day 1 up to Month 6
Pharmacokinetic (PK) Profile Of Natalizumab
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BG00002 (natalizumab) in people with Multiple Myeloma, run by Biogen at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Day 1 up to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2014.