Relapsed or Relapsed and Refractory Multiple Myeloma (MM) MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000054086
Conditions
Interventions
Product Name: Ibrutinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Current Sponsor code:
Sponsors
Pharmacyclics Switzerland GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with MM who have received 2-3 prior lines of therapy and have demonstrated disease progression since the completion of the most recent treatment regimen. 2. Measurable disease defined by at least ONE of the following: • Serum monoclonal protein (SPEP) =1 g/dL • Urine monoclonal protein (UPEP) =200 mg by 24 hour urine electrophoresis 3. Adequate hematologic function 4. Adequate hepatic and renal function 5. Prothrombin time (PT)/ International normal ratio (INR) =1.5 x upper limit of normal (ULN) and PTT (activated partial thromboplastin time [aPTT]) =1.5 x ULN 6. Male and female =18 years of age 7. Eastern Cooperative Oncology Group (ECOG) performance status of =2. 8. Male and female subjects of reproductive potential who agree to use highly effective methods of birth control during the period of therapy and for 90 days after the last dose of study treatment. Female subjects who are of non-reproductive potential. Female subjects of reproductive potential must have a negative serum pregnancy test upon study entry. Other protocol-defined inclusion criteria could apply Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Primary refractory disease defined as nonresponsive in patients who have never achieved a minimal response or better with any therapy. 2. History of plasma cell leukemia, primary amyloidosis, POEMS syndrome within 12 months prior to first administration of study treatment. 3. Recent prior chemotherapy 4. Prior exposure to BTK inhibitors 5. Refractory or non-responsive to prior PI therapy (bortezomib or carfilzomib) 6. History of hypersensitivity reactions to prior bortezomib, to boron, mannitol or nitrogen. 7. History of other malignancies 8. Peripheral neuropathy Grade =2 or Grade 1 with pain at Screening 9. Prior allogeneic stem cell transplant 10. Recent infection requiring systemic treatment that was completed <7 days before the first administration of study treatment and/or uncontrolled active systemic infection. 11. Unresolved toxicities from prior anti-cancer therapy 12. Known bleeding disorders (eg, von Willebrand’s disease or hemophilia) 13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 14. Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV) 15. Major surgery within 4 weeks of first administration of study treatment. 16. Any life-threatening illness, medical condition, including uncontrolled Diabetes Mellitus, or organ system dysfunction 17. Currently active, clinically significant hepatic impairment 18. Currently active, clinically significant cardiovascular disease 19. Unable to swallow capsules or malabsorption syndrome 20. Subjects who received a strong cytochrome P (CYP) 450 3A inhibitor within 7 days prior to the first administration of study treatment or subjects who require continuous treatment with a strong CYP 3A inhibitor 21. Lactating or pregnant Other protocol-defined exclusion criteria could apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate Progression-Free Survival (PFS) according to International Myeloma Working Group (IMWG) response criteria (Rajkumar 2011) in subjects with relapsed or relapsed and refractory MM.;Timepoint(s) of evaluation of this end point: The primary analysis is planned to include data up to 12 months after the last subject is enrolled or 83 PFS events, whichever occur earlier. This is estimated to occur Q3 2019.; Secondary Objective: • Overall Response Rate (=PR) • PFS Rate at Landmark Points • Duration of Response (DOR) • Overall Survival (OS) • Time to Progression (TTP) • To evaluate the safety and tolerability of ibrutinib in combination with bortezomib and dexamethasone. ;Primary end point(s): The primary efficacy endpoint of this study is mPFS. Progression free survival is defined as the time from the date of first dose of study treatment to confirmed disease progression or death from any cause, whichever occurs first. The mPFS is the time at which the percentage or probability of surviving and progression-free is 50%. The mPFS will be assessed according to the IMWG response criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR is the proportion of subjects who achieve a PR or better over the course of the study but prior to initiation of subsequent anti-cancer therapy. • PFS rates at landmark points are the percentages or probabilities of surviving and progression-free at the landmark time points. The landmark time points will be described further in the SAP. • The DOR is defined as the interval between the date of initial documentation of a response and the date of first documented evidence of progressive disease, death, or date of censoring if applicable, for responders only. Responders are subjects in the ITT population who achieve PR or better according to the IMWG response criteria. Non responders (=PR) will be excluded from the analysis for DOR. • OS is defined as the time from the date of first dose of study treatment until date of death due to any cause. • TTP is defined as the time from the start of treatment until date of disease progression. Subjects who die due to causes other than disease progression will be censored at the date of death. ;Timepoint(s) of evaluation of this end point: The analysis of secondary endpoints will also occur at the time of the primary analysis. In addition, a final analysis will occur at the time of study closure and may include updates to the secondary endpoints as applicable for those subjects either continuing on treatment at the time of the primary analysis or those that have discontinued treatment but not yet experienced an event (progression or death). | — |
Countries
Czech Republic, France, Germany, Greece, Italy, Poland, Spain, Turkey
Contacts
Public ContactMedical Monitor - Edyta Dobkowska
Pharmacyclics Switzerland GmbH
Outcome results
None listed