A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 79
- Locations
- 1
- Primary Endpoint
- Estimate the MTD and/or RDE
Overview
Brief 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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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
Exclusion Criteria
- •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.
Arms & Interventions
LGH447
Eligible patients will be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity.
Intervention: LGH447 (Drug)
LGH447 and midazolam
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.
Intervention: LGH447 (Drug)
LGH447 and midazolam
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.
Intervention: midazolam (Drug)
Outcomes
Primary Outcomes
Estimate the MTD and/or RDE
Time Frame: 12 months
Incidence rate of dose limiting toxicity
Secondary Outcomes
- Number of participants with adverse events and serious adverse events.(18 months)
- Anti-Myeloma activity associated with LGH447(18 months)
- Pharmacokinetic (PK) effects of LGH447(18 months)
- Pharmacodynamic (PD) effects of LGH447(18 months)
- Effect of multiple-doses of LGH447 on the PK of midazolam(6 months)