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

Phase 1

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: CPI-0610

• Registration Number: NCT02157636
• Lead Sponsor: Constellation Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-05-28
• Study First Submitted QC: 2014-06-04
• Study First Posted: 2014-06-06
• Study Start: 2014-07-15
• Primary Completion: 2016-11-08
• Study Completion: 2016-11-08
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-17
• Last Update Posted: 2024-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• 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 the 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
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
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
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	This outcome measure is a composite measure
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	Anti-myeloma activity will be assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma