A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma

NCT02157636 | Completed Phase 1

• 1 other identifier: 0610-03
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Myeloma

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 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

• 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

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 or cytologically confirmed diagnosis of multiple myeloma that has progressed despite at least one line of standard therapy
• 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
• 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:

• Current infection with HIV, Hepatitis B or Hepatitis C
• 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) \< 50%
• 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
• 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 myeloma, 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

Sponsors & Collaborators

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

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

CPI-0610

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; 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: May 28, 2014
• First Posted: June 6, 2014
• Study Start: July 15, 2014
• Primary Completion: November 8, 2016
• Study Completion: November 8, 2016
• Last Updated: April 18, 2024

Record last verified: 2024-04