Clinical trial NCT02157636: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Phase 1
Oncology
BET Inhibitor
Lead sponsor: Constellation Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Leukemia and Lymphoma Society
First posted: 2014-06-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment
timeFrame: DLTs asessed during Cycle 1 (first 21 days on study)
Secondary outcomes:
measure: 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
timeFrame: Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug
measure: Pharmacokinetic parameters of CPI-0610: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F
timeFrame: Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1
measure: 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
timeFrame: Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1
measure: Changes in the expression of a set of genes in peripheral blood mononuclear cells (PBMCs) that are sensitive to BET inhibition
timeFrame: Assessed during cycle 1 (first 21 days on study)
measure: Anti-myeloma activity associated with CPI-0610 treatment
timeFrame: Assessed after every cycle of treatment; assessed up to approximately 12 months
Other outcomes:
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