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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01949883
• Other study ID #: 0610-01
• Status: Completed
• Phase: Phase 1
• Start date: September 5, 2013
• Est. completion date: December 20, 2017

Study information

• Verified date: May 2024
• Source: Constellation Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: December 20, 2017
• Est. primary completion date: December 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• CPI-0610

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Constellation Pharmaceuticals	The Leukemia and Lymphoma Society

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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