A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CPI-0610
|
Drug: CPI-0610
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
- 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]
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults (aged ≥ 18 years)
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Histologically or cytologically confirmed diagnosis of multiple myeloma that has progressed despite at least one line of standard therapy
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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
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Adequate hematological, renal, hepatic, and coagulation laboratory assessments
-
Written informed consent to participate in this study before the performance of any study-related procedure
Exclusion Criteria:
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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:
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Acute myocardial infarction or angina pectoris ≤ 6 months prior to starting study drug
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Serum cardiac troponin (cTn) level ≥ 99% percentile of the upper reference limit
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QTcF > 470 msec on the screening ECG
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Constellation Pharmaceuticals
- The Leukemia and Lymphoma Society
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0610-03