A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
CPI-0610
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Phase 1, Oncology, BET Inhibitor
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CPI-0610
Arm Description
Outcomes
Primary Outcome Measures
Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment
Secondary Outcome Measures
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
Pharmacokinetic parameters of CPI-0610: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F
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
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
Anti-myeloma activity associated with CPI-0610 treatment
Anti-myeloma activity will be assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma
Full Information
NCT ID
NCT02157636
First Posted
May 28, 2014
Last Updated
May 16, 2022
Sponsor
Constellation Pharmaceuticals
Collaborators
The Leukemia and Lymphoma Society
1. Study Identification
Unique Protocol Identification Number
NCT02157636
Brief Title
A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma
Official Title
A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Previously Treated Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
July 2014 (Actual)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Constellation Pharmaceuticals
Collaborators
The Leukemia and Lymphoma Society
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Phase 1, Oncology, BET Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CPI-0610
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CPI-0610
Primary Outcome Measure Information:
Title
Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment
Time Frame
DLTs asessed during Cycle 1 (first 21 days on study)
Secondary Outcome Measure Information:
Title
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
Time Frame
Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug
Title
Pharmacokinetic parameters of CPI-0610: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F
Time Frame
Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1
Title
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
Description
This outcome measure is a composite measure
Time Frame
Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1
Title
Changes in the expression of a set of genes in peripheral blood mononuclear cells (PBMCs) that are sensitive to BET inhibition
Time Frame
Assessed during cycle 1 (first 21 days on study)
Title
Anti-myeloma activity associated with CPI-0610 treatment
Description
Anti-myeloma activity will be assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma
Time Frame
Assessed after every cycle of treatment; assessed up to approximately 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Learn more about this trial
A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma
We'll reach out to this number within 24 hrs