A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma

Study Overview
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Brief Summary
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First in human, open-label, sequential dose escalation and expansion study of CPI-0610 in patients with progressive lymphoma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Official Title
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A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Progressive Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: CPI-0610


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (aged ≥ 18 years) Histologically confirmed diagnosis of a non-Hodgkin or Hodgkin lymphoma that has progressed in spite of prior treatment, and for which additional effective standard therapy is not available Patients may have either measurable or non-measurable disease, but in all cases eligible patients must have disease that can be clinically evaluated for improvement or progression 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 Exclusion Criteria: A primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of the CNS. CNS imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the CNS. Current infection with HIV, Hepatitis B or Hepatitis C. Patients will have serologic testing performed during screening for HIV and Hepatitis B and C. Any serologic results suggestive of an ongoing viral infection will be further investigated as necessary to clarify the patient's status. 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. 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) < 40% Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded.) 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) Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of CPI-0610 Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks before the first dose of CPI-0610 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. 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 or aggressive subtypes of lymphoma following discussion with the medical monitor. Treatment with medications that are known to be strong inhibitors or inducers of CYP450 enzymes. Treatment with medications that are known to carry a risk of Torsades de Pointes. 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. Pregnant or lactating women 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 Patients unwilling or unable to comply with this study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-0610<br> | Drug: CPI-0610<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 tumor tissue; changes in cellular proliferation and in the extent of apoptosis; changes in tumor metabolism |  | Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1 | 
| 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-lymphoma activity associated with CPI-0610 treatment |  | After every 2 cycles of treatment for the first 6 cycles, and after every 4 cycles thereafter; assessed up to approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Oncology, BET Inhibitor