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

Phase 1

Completed

• Conditions: Lymphoma
• Interventions: Drug: CPI-0610

• Registration Number: NCT01949883
• Lead Sponsor: Constellation Pharmaceuticals

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-05
• Study First Submitted: 2013-09-10
• Study First Submitted QC: 2013-09-24
• Study First Posted: 2013-09-25
• Primary Completion: 2017-12-20
• Study Completion: 2017-12-20
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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

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
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
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
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