A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma
- Registration Number
- NCT02157636
- Lead Sponsor
- Constellation Pharmaceuticals
- Brief Summary
Open-label, sequential dose escalation and expansion study of CPI-0610 in patients with previously treated multiple myeloma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
- Adults (aged ≥ 18 years)
- Histologically or cytologically confirmed diagnosis of multiple myeloma that has progressed despite at least one line of standard therapy
- Must have measurable disease, defined by one or more of following: (i) a serum M protein > 0.5 g/dl measured by serum protein electrophoresis; (ii) urinary M protein excretion > 200 mg/24 hours; (iii) serum free light chain (FLC) measurement > 10 mg/dl, provided that the serum FLC ratio is abnormal
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Adequate hematological, renal, hepatic, and coagulation laboratory assessments
- Written informed consent to participate in this study before the performance of any study-related procedure
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Current infection with HIV, Hepatitis B or Hepatitis C
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Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of CPI-0610, including any unresolved nausea, vomiting, or diarrhea that is CTCAE grade >1
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Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Acute myocardial infarction or angina pectoris ≤ 6 months prior to starting study drug
- Serum cardiac troponin (cTn) level ≥ 99% percentile of the upper reference limit
- QTcF > 470 msec on the screening ECG
- Left ventricular ejection fraction (LVEF) < 50%
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Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded.)
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Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
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Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of CPI-0610
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Treatment with an investigational small molecule less than 2 weeks before the first dose of CPI-0610. In addition, the first dose of CPI-0610 should not occur before a period equal to or greater than 5 half-lives of the small molecule investigational agent has elapsed
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Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-0610. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive myeloma, following discussion with the medical monitor
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Treatment with medications that are known to be strong inhibitors or inducers of CYP450 enzymes
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Treatment with medications that are known to carry a risk of Torsades de Pointes
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Immunosuppressive treatment that cannot be discontinued both prior to study entry and for the duration of the study. Oral prednisone at a dose of 10 mg or less per day is allowed, as are other oral corticosteroids given at glucocorticoid-equivalent doses. Topical, nasal and inhaled corticosteroids are also allowed
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Pregnant or lactating women
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Women of child-bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter
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Patients unwilling or unable to comply with the study protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CPI-0610 CPI-0610 -
- Primary Outcome Measures
Name Time Method Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment DLTs asessed during Cycle 1 (first 21 days on study)
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameters of CPI-0610: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1 Safety and tolerability of CPI-0610 as assessed by: frequency of adverse events and serious adverse events; changes in hematology and clinical chemistry values; changes in physical examination, vital signs, electrocardiogram, ECHO and ECOG score Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug Pharmacodynamic effects of CPI-0610: Changes in the expression of MYC and other genes in malignant tumor cells; changes in cellular proliferation and in the extent of apoptosis Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1 This outcome measure is a composite measure
Changes in the expression of a set of genes in peripheral blood mononuclear cells (PBMCs) that are sensitive to BET inhibition Assessed during cycle 1 (first 21 days on study) Anti-myeloma activity associated with CPI-0610 treatment Assessed after every cycle of treatment; assessed up to approximately 12 months Anti-myeloma activity will be assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma
Related Research Topics
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