Relapsed or refractory mantle cell lymphoma MedDRA version: 14.1 Level: PT Classification code 10026801 Term: Mantle cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10026800 Term: Mantle cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PCI-32765-00
Product Code: PCI-32765-00
Pharmaceutical Form: Capsule, hard
CAS Number: 936563-96-1
Current Sponsor code: PCI-32765-00
Other descriptive name: 1-[(3R)-3-[4-amino-3-(4-phe
Sponsors
Pharmacyclics, Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women = 18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status of = 2 3. Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11;14), and measurable disease on cross sectional imaging that is = 2 cm in the longest diameter and measurable in 2 perpendicular dimensions per CT 4. Documented failure to achieve at least PR with, or documented disease progression after, the most recent treatment regimen 5. At least 1, but no more than 5, prior treatment regimens for MCL. (Note: Subjects having received = 2 cycles of prior treatment with bortezomib, either as a single agent or as part of a combination therapy regimen, will be considered to be bortezomib-exposed.) 6. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty 7. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy within 3 weeks, or major surgery within 2 weeks of first dose of study drug 2. Concurrent enrollment in another therapeutic investigational clinical study or have previously taken PCI-32765. 3. History of other malignancies within the past year except for treated basal cell or squamous cell skin cancer or in situ cervical cancer 4. Known central nervous system (CNS) lymphoma 5. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk 6. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification 7. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, or QTc = 500 msec 8. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or symptomatic ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction 9. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection 10. Lactating or pregnant 11. Will not agree to use highly effective contraception (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the study and for 30 days after the last dose of study drug (Note: applies to men and women of child-bearing potential only) 12. Any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) 2.0 x ULN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to evaluate the efficacy of PCI-32765 in relapsed/refractory subjects with MCL;Secondary Objective: The secondary objective is to evaluate the safety of a fixed daily dosing regimen of PCI-32765 capsules in relapsed/refractory subjects with MCL.;Primary end point(s): The primary endpoint of the study is the ORR defined as a subject achieving either a PR or CR according to the revised International Working Group Criteria for NHL as assessed by investigators.;Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed throughout the duration of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints for this study are as follows: Efficacy: - duration of response (DOR) - progression-free survival (PFS) - overall survival (OS) Safety: - frequency, severity, and relatedness of adverse events - frequency of adverse events requiring discontinuation of study drug or dose reductions - effect of PCI-32765 on peripheral B/T/NK cell counts - effect of PCI-32765 on serum immunoglobulin levels Pharmacokinetics: - plasma PK of PCI-32765 and a major metabolite, PCI-45227 Patient Reported Outcomes: - health-related quality of life;Timepoint(s) of evaluation of this end point: Secondary endpoints will be assessed throughout the duration of the study. | — |
Countries
Austria, Germany, Poland, United Kingdom, United States
Contacts
Public ContactSusanne Fitzsimons
inVentiv Health Clinical UK Limited
Outcome results
None listed