Phase 2
N=25
SMAC Mimetic LCL161 Alone or With Cyclophosphamide in Treating Patients With Relapsed or Refractory Multiple Myeloma
Recurrent Plasma Cell Myeloma · Refractory Plasma Cell Myeloma
Bottom Line
View on ClinicalTrials.gov: NCT01955434 ↗Enrolled (actual)
25
Serious AEs
44.0%
Results posted
Feb 2018
Primary outcome: Primary: Confirmed Overall Response Rate (Stringent Complete Response [sCR], Complete Response [CR], Very Good Partial Response [VGPR], or Partial Response [PR]) With Single Agent SMAC Mimetic LCL161 — 0 percentage of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cyclophosphamide (Drug); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Quality-of-Life Assessment (Other); Smac Mimetic LCL161 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Mayo Clinic
- Primary completion
- Jun 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Confirmed Overall Response Rate (Stringent Complete Response [sCR], Complete Response [CR], Very Good Partial Response [VGPR], or Partial Response [PR]) With Single Agent SMAC Mimetic LCL161 |
— | — |
| SECONDARY Combination Agent Response Rate |
17.4 | — |
| SECONDARY Event-free Survival |
10.0 | — |
| SECONDARY Incidence of Toxicities Graded Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (All Treatment) |
24; 16; 4.0; 12.0; 36.0; 52.0 | — |
| SECONDARY Overall Survival |
NA | — |
Summary
This phase II trial studies how well second mitochondrial-derived activator of caspases (SMAC) mimetic LCL161 alone or with cyclophosphamide works in treating patients with multiple myeloma that has returned or does not respond to treatment. Biological therapies, such as SMAC mimetic LCL161, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving SMAC mimetic LCL161 alone or with cyclophosphamide is more effective in treating multiple myeloma.
Eligibility Criteria
Inclusion Criteria
- Relapsed or refractory multiple myeloma and has already received = = 1000/uL
- Untransfused platelet count >= 75,000/uL
- Aspartate aminotransferase (AST) = = 8 g/dL
- Measurable disease of multiple myeloma as defined by at least ONE of the following:
- Serum monoclonal protein >= 1.0 g/dL
- >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Monoclonal plasmacytosis >= 30% (evaluable disease)
- Measurable plasmacytoma that has not been radiated
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
- Willing and able to comply with scheduled visits, treatment plan and laboratory tests
- Able to swallow and retain oral medication
- Provide informed written consent
- Negative serum pregnancy test done = 100 bpm) (NOTE: patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria)
- Clinically significant resting bradycardia (< 50 bpm)
- Angina pectoris or acute myocardial infarction =< 3 months prior to registration
- Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
- Currently receiving treatment with agents that are metabolized solely through cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates; caution should be used in patients taking other CYP2C8- or CYP3A4/5-interacting agents
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LCL161
Data sourced from ClinicalTrials.gov (NCT01955434). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.