Multiple MyelomaPhase 1NCT01456689
A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
A Phase 1 study testing LGH447 and midazolam in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 8 sites in 4 countries.
Trial summary
The primary purpose of this dose escalation study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LGH447 as a single agent when administered orally once daily to adult patients with Multiple Myeloma (MM). 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?
- LGH447 and midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 25 Apr 2012to 5 Jun 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Confirmed diagnosis of multiple myeloma that is relapsed and/or refractory for which no curative option exists.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- During the dose expansion part of the study patients must have measurable disease defined by at least 1 of the following 2 measurements:
- Serum M-protein ≥ 0.5 g/dL
- Urine M-protein ≥ 200 mg/24 hours
- Serum free light chain (FLC) > 100 mg/L of involved FLC
Who cannot join
- Patients who are currently receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with LGH447:
- Strong inhibitors or inducers of CYP3A4
- CYP3A4 substrates with narrow therapeutic index
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States4 sites
Novartis Investigative Site
Ann Arbor, Michigan, 48109
Novartis Investigative Site
Chicago, Illinois, 60637
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Rochester, Minnesota, 55905
Germany2 sites
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Kiel, 24105
About this study
Official title: A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
The primary purpose of this dose escalation study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LGH447 as a single agent when administered orally once daily to adult patients with Multiple Myeloma (MM).
- Conditions
- Multiple Myeloma
- Being tested
- LGH447, midazolam
- Keywords
- Myeloma, Multiple Myeloma, MM
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LGH447Drug
midazolamDrug
| Study group | Role | What they receive |
|---|---|---|
| LGH447 | Experimental | Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. Receives: Drug: LGH447 |
| LGH447 and midazolam | Experimental | Eligible patients will receive midazolam on two separate days, the first dose will be administered prior to the start of LGH447 and the second will be co-administered with LGH447. After that, the patients will continue to be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. Receives: Drug: LGH447; Drug: midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the MTD and/or RDE
Incidence rate of dose limiting toxicity
Measured: 12 months
Secondary outcomes (5)
Number of participants with adverse events and serious adverse events.
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Measured: 18 months
Pharmacokinetic (PK) effects of LGH447
Summary of PK parameters such as AUC, Cmax,
Measured: 18 months
Pharmacodynamic (PD) effects of LGH447
Changes between pre and post treatment levels in bone marrow aspirates and whole blood.
Measured: 18 months
Anti-Myeloma activity associated with LGH447
Overall Response Rate (ORR), Duration of Response (DOR), and Progression Free Survival (PFS) based on International Myeloma Working Group Response Criteria.
Measured: 18 months
Effect of multiple-doses of LGH447 on the PK of midazolam
PK parameters of midazolam and 1-hydroxymidazolam, such as AUC and Cmax, as well as metabolic ratio of midazolam.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2011 (estimated)
- Study start25 Apr 2012
- Primary completion5 Jun 2019
- Study completion5 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01456689
- Sponsor's protocol ID
- CLGH447X2101
- Other IDs
- 2011-003820-10
- Status last verified
- Oct 2019
- First submitted
- 11 Oct 2011
- Last updated
- 17 Dec 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01456689
- Acronym / sponsor ID
- CLGH447X2101
- Conditions
- Multiple Myeloma
- Keywords
- Myeloma, Multiple Myeloma, MM
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2012 (actual)
- Primary completion
- 5 Jun 2019 (actual)
- Study completion
- 5 Jun 2019 (actual)
- First posted
- 21 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this dose escalation study is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LGH447 as a single agent when administered orally once daily to adult patients with Multiple Myeloma (MM).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LGH447 | Experimental | Drug: LGH447Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. |
| LGH447 and midazolam | Experimental | Drug: LGH447, Drug: midazolamEligible patients will receive midazolam on two separate days, the first dose will be administered prior to the start of LGH447 and the second will be co-administered with LGH447. After that, the patients will continue to be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Confirmed diagnosis of multiple myeloma that is relapsed and/or refractory for which no curative option exists.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- During the dose expansion part of the study patients must have measurable disease defined by at least 1 of the following 2 measurements:
Key exclusion criteria (4 listed)
- Patients who are currently receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with LGH447:
- Other protocol-defined inclusion/exclusion criteria may apply.
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 |
|---|---|---|
| LGH447 | Drug | LGH447, LGH447 and midazolam |
| midazolam | Drug | LGH447 and midazolam |
Primary outcome
Estimate the MTD and/or RDE
Time frame: 12 months
Incidence rate of dose limiting toxicity
5 secondary outcomes
Number of participants with adverse events and serious adverse events.
Time frame: 18 months
Pharmacokinetic (PK) effects of LGH447
Time frame: 18 months
Pharmacodynamic (PD) effects of LGH447
Time frame: 18 months
Anti-Myeloma activity associated with LGH447
Time frame: 18 months
Effect of multiple-doses of LGH447 on the PK of midazolam
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Results for CLGH447X2101 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LGH447 and midazolam in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 8 sites in 4 countries.
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 6 inclusion and 4 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: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Germany, Singapore, Spain. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Estimate the MTD and/or RDE (time frame: 12 months). 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 17 Dec 2020.