A clinical study to investigate the efficacy and safety of copanlisib inpatients with relapsed or refractory diffuse large B-cell lymphoma.
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]patients with relapsed or refractory diffuse large B cell lymphoma
- Registration Number
- EUCTR2014-004848-36-DK
- Lead Sponsor
- Bayer HealthCare AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 66
1. Ability to understand and willingness to sign written informed consent. Signed informed consent (including consent to genetic analysis) must be obtained before any study specific procedure.
2. Male or female patients age = 18 years old.
3. Diagnosis of DLBCL (de novo or DLBCL transformed from follicular lymphoma on the basis of a tissue biopsy). Pathology and immunohistochemistry reports documenting the current histological
diagnosis of DLBCL or DLBCL transformed from follicular lymphoma according to WHO classification must be reviewed by the sponsor or designee prior to enrollment.
• DLBCL not otherwise specified (NOS)
• T-cell/histiocyte-rich large B-cell lymphoma
• Epstein-Barr virus (EBV) positive DLBCL of the elderly
4. Received at least one prior therapy for aggressive NHL (DLBCL).
5. Received CHOP + rituximab or equivalent regimen (addition of etoposide or substitution of idarubicin, epirubicin, or mitoxantrone for doxorubicin is allowed) for NHL.
7. Patients must have measurable disease (at least one bidimensionally measurable site of disease that has not been previously irradiated: nodal disease >1.5 cm or an extranodal lesion > 1.0 cm in longest
perpendicular diameter). Lesion must be PET-positive if a PET scan is obtained.
8. Not eligible or not willing to receive the high-dose (myeloablative) chemotherapy (HDC) and SCT.
9. A fresh tumor biopsy collected during screening and /or archival tumor tissue collected after the last relapse/disease progression (material which has been collected before the last line of treatment is
not accepted). In addition, a sufficient amount of the material is required for acceptance of the archival material. If neither condition occurs a fresh tumor biopsy needs to be performed as stated above.
10. ECOG performance status (PS) = 2
11. Life expectancy = 12 weeks in investigator's judgment
12. Left ventricular ejection fraction (LVEF) = the lower limit of normal (LLN) for the Institution (as per local standard of care) as measured by ECHO (echocardiogram) or Multiple gated acquisition (MUGA) scan
13. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days before start of study treatment:
- Hemoglobin = 8 g/dL
- Platelet count = 100 x 109L/; platelet count = 75 x 109/L permitted if documented bone marrow involvement
- Absolute neutrophil count (ANC) = 1.5 x 109/L; ANC = 1.0 x 109/L permitted if documented bone marrow involvement
- Total bilirubin = 1.5 x upper limit of normal (ULN); patients with proven Gilbert's syndrome and total bilirubin = 5 x ULN may be enrolled.
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2 x ULN, or = 5 x ULN if elevation is due to hepatic involvement by lymphoma
- Glomerular filtration rate (GFR) = 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula (See Appendix 16.4).
- International normalized ratio (INR) and partial thromboplastin time (PTT) = 1.5 x ULN. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring is recommended according to the local standard of care.
- Lipase < 1.5 x the ULN
14. Willingness and ability to comply with the visit schedule and assessments required by the study protocol
15. Women of childbearing potential
1. Previous assignment to treatment during this study. Patients
permanently withdrawn from study participation will not be allowed to
re-enter the study.
2. Concurrent participation in other clinical studies. Patients must
complete their participation in another clinical study with an
investigational medicinal product 28 days before the start of treatment
or 5 half-lives of the investigational treatment, whichever is longer.
3. Patients who previously received therapy with copanlisib or other
PI3K inhibitors are not eligible for enrollment.
4. Close affiliation with the investigational site; e.g. a close relative of
the investigator, dependent person (e.g. employee or student of the
investigational site)
Excluded medical conditions
5. Any of the following as the only site(s) of disease: palpable lymph
nodes not visible on imaging studies, skin lesions, or bone marrow
involvement only.
6. Active CTCAE Grade 3/4 infection
7. Hepatitis B (HBV) or hepatitis C (HCV). All patients must be screened
for HBV and HCV up to 28 days prior to study drug start using the routine
hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb
will be eligible if they are negative for HBV-DNA; patients positive for
anti-HCV will be eligible if they are negative for HCV-RNA
8. Known history of human immunodeficiency virus (HIV) infection
9. Current central nervous system (CNS) involvement by lymphoma
- Any past history or evidence of current leptomeningeal involvement by
lymphoma is prohibited.
- Patients with prior localized CNS involvement who have been without
recurrence for = 12 mths and currently have a negative head MRI and
negative cerebrospinal fluid (CSF) may be eligible.
10. Unstable angina (angina symptoms at rest), new-onset angina
(begun within the last 3 mths). Myocardial infarction within the past 6
months before start of study treatment
11. Uncontrolled arterial hypertension despite optimal medical
Management (per investigator's opinion).
12. Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.
13. New York Heart Association (NYHA) class III or IV heart disease.
14. Any other malignancy within last 3 yrs except for the following,
which are permitted:
a. curatively treated non-melanoma skin cancer
b. carcinoma in situ of the cervix
c. in situ ductal carcinoma of the breast after complete resection
d. superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma
in situ] and T1 [tumor invades lamina propria])
15. Any illness or conditions (substance abuse, medical, psychological or
social) that may interfere with the patient's participation in the study,
evaluation of the study results, or could jeopardize the safety of the
patient and his/her compliance in the study.
16. Non-healing wound ulcer or bone fracture.
17. Major surgical procedure or significant traumatic injury (as judged
by the investigator) less than 28 days before start of study treatment.
18. Patients with seizure disorder requiring medication.
19. Patients with evidence or history of bleeding diathesis. Any
hemorrhage or bleeding event with CTCAE Grade = 3 within 4 weeks
prior to screening.
20. Proteinuria of CTCAE Grade 3 or higher (> 3.5 measured by urine
protein to creatinine ratio on a random urine sample)
21. History or concurrent condition of interstitial lung disease of any
severity and/or severely impaired lung function (as judged by the
investigator).
22. Pregnant or breast-feeding
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