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

NCT01949883 | Completed Phase 1

• 1 other identifier: 0610-01
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lymphoma

Keywords

Phase 1; Oncology; BET Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (1)

CPI-0610

EXPERIMENTAL

Drug: CPI-0610

Interventions

CPI-0610 DRUG

CPI-0610

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Constellation Pharmaceuticals: lead
• The Leukemia and Lymphoma Society: collaborator

Related Publications (1)

• Blum KA, Supko JG, Maris MB, Flinn IW, Goy A, Younes A, Bobba S, Senderowicz AM, Efuni S, Rippley R, Colak G, Trojer P, Abramson JS. A Phase I Study of Pelabresib (CPI-0610), a Small-Molecule Inhibitor of BET Proteins, in Patients with Relapsed or Refractory Lymphoma. Cancer Res Commun. 2022 Aug 11;2(8):795-805. doi: 10.1158/2767-9764.CRC-22-0060. eCollection 2022 Aug.

  PMID: 36923307 DERIVED

MeSH Terms

Conditions

Lymphoma; Neoplasms

Interventions

CPI-0610

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 25, 2013
• Study Start: September 5, 2013
• Primary Completion: December 20, 2017
• Study Completion: December 20, 2017
• Last Updated: May 8, 2024

Record last verified: 2024-05