A clinical study of Ibrutinib taken together with Pomalidomide and Dexamethasone in patients with Multiple Myeloma (who have stopped responding or have failed to respond to current treatments)
- Conditions
- Relapsed/Refractory Multiple MyelomaMedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2015-002191-25-DE
- Lead Sponsor
- Pharmacyclics LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 11
Disease Related
1. Subjects with relapsed/refractory MM who have received at least two prior lines of therapy including LEN and either bortezomib or carfilzomib and have demonstrated disease progression on or within 60 days of the completion of the most recent treatment regimen.
- Subjects must have received at least 2 cycles of treatment with LEN and either bortezomib or carfilzomib at the approved dose and schedule (maintenance will be excluded).
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.
Laboratory
3. Adequate hematologic function independent of platelet transfusion and growth factor support for at least 7 days prior to Screening and dosing (Phase 1) or randomization/enrollment (Phase 2b), with the exception of pegylated G-CSF (granulocyte-colony stimulating factor pegfilgrastim) and darbopoeitin which require at least 14 days, defined as:
• Absolute neutrophil count =1500 cells/mm^3(1.5 x 10^9/L).
• Platelet count >75,000 cells/mm^3 (75 x 109/L).
• Hemoglobin =8.0 g/dL.
4. Adequate hepatic and renal function defined as:
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) =3.0 x upper limit of normal (ULN).
• Serum creatinine <3.0 mg/dL AND Creatinine Clearance =30 mL/min (by Cockcroft-Gault OR as measured by 24 hour urine collection).
• Total Bilirubin =2.0 mg/dL.
5. PT/INR =1.5 x ULN and PTT (aPTT) =1.5 x ULN (unless on warfarin, then INR =3.0).
Demographic
6. Men and women = 18 years of age.
7. Eastern Cooperative Oncology Group (ECOG) performance status of =2.
Ethical/Other
8. All study participants must be registered into the mandatory Pomalyst REMS™ or RevAid® program, and be willing and able to comply with the requirements of the Pomalyst REMS™ or RevAid® program as appropriate for the country in which the drug is being used. (for US/Canada Sites Only).
9. Female subjects of childbearing potential (FCBP)a must adhere to the scheduled pregnancy testing as required in the Pomalyst REMS™ or RevAid® program as appropriate for the country in which the drug is being used. (for US/Canada Sites Only).
10. Female subjects of childbearing potential (FCBP)a must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days and again within 24 hours prior to starting Cycle 1 of pomalidomide. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure (for ex US sites only).
11. Male subjects must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. (for US/Canada sites only).
12. Male subjects must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure, (for ex US sites only).
13. FCBP and male subjects who are sexually
Disease-Related
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.
Concurrent Conditions
3. Recent prior chemotherapy
a. Alkylators (eg, melphalan, cyclophosphamide) and/or anthracyclines =21 days prior to first administration of study treatment.
b. High dose corticosteroids, IMiDs or proteasome inhibitors =14 days prior to first administration of study treatment.
c. Monoclonal antibody =6 weeks prior to first administration of study treatment.
4. Prior exposure to Bruton’s tyrosine kinase (BTK) inhibitors.
5. Prior exposure to pomalidomide (except Treatment Arm C).
6. History of serious hypersensitivity reactions to prior thalidomide, lenalidomide or pomalidomide.
7. History of other malignancies, except:
a. Malignancy treated with curative intent and with no known active disease present for =3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
c. Adequately treated carcinoma in situ without evidence of disease.
8. Peripheral neuropathy Grade =2 with pain at Screening.
9. Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >20 mg/day of prednisone or equivalent) within 28 days of the first dose of study treatment.
10. Recent infection requiring systemic treatment that was completed =7 days before the first dose of study treatment and/or uncontrolled active systemic infection.
11. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), Grade =1 or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
12. Known bleeding disorders (eg, von Willebrand’s disease or hemophilia).
13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment/randomization.
14. Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment/ randomization. Those who are PCR positive will be excluded.
15. Major surgery within 4 weeks of first dose of study treatment.
16. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk.
17. Currently active, clinically significant hepatic impairment (= mild hepatic impairment according to the Child Pugh classification.
18. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrh
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method