A study investigating copanlisib in combination with standard treatment versus standard treatment alone in order to see if copanlisib improves the response to standard treatment in patients with relapsed indolent non-Hodgkin's lymphoma.
- Conditions
- Patients with relapsed indolent non-Hodgkin's lymphomaMedDRA version: 20.0Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-001088-38-GB
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 520
Main criteria for inclusion:
- Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to:
o Follicular lymphoma (FL) G1, G2, or G3a
o Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5x109/L at study entry
o Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM)
o Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
-- Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab-based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab can be considered a previous regimen in the case the patient responded to it); at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to other PI3K inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or PD after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor.
- Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
- Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level = 2 x upper limit of normal and positive immunofixation test.
- Male or female patients = 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status = 2.
- Life expectancy of at least 3 months.
- Availability of fresh tumor tissue and/or archival tumor tissue at Screening.
- Women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the informed consent form and 12 months (for WOCBP) and 6 months (for men) after the last administration of study treatment. The use of condoms by male patients is required unless the female partner is permanently sterile.
- Adequate baseline laboratory values as assessed within 7 days before starting study treatment.
- Left ventricular ejection fraction = 50%.
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 206
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 206
Main criteria for exclusion:
- Histologically confirmed diagnosis of follicular lymphoma (FL) grade 3b
or transformed disease, or chronic lymphocytic leukemia. In patients
with clinical suspicion of transformed disease, a fresh biopsy is
recommended.
- Rituximab resistance at any line of therapy (resistance defined as lack
of response, or progression within 6 months of the last date of rituximab administration, including rituximab maintenance).
- History or concurrent condition of interstitial lung disease and/or
severely impaired lung function (as judged by the investigator).
- Known lymphomatous involvement of the central nervous system.
- HbA1c > 8.5% at Screening.
- Known history of human immunodeficiency virus (HIV) infection.
- Hepatitis B (HBV) or C (HCV) infection. Patients positive for hepatitis B
surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be
eligible if they are negative for HBV-DNA, these patients should receive
prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
- Previous or concurrent history of malignancies other than indolent non-
Hodgkin's lymphoma within 5 years prior to study treatment except for
curatively treated: Cervical carcinoma in situ, Non-melanoma skin
cancer, Superficial bladder cancer (Ta [non-invasive tumor], Tis
[carcinoma in situ] and T1 [tumor invades lamina propria]), Localized
prostate cancer
- Congestive heart failure > New York Heart Association (NYHA) class 2.
- Unstable angina (angina symptoms at rest), new-onset angina (begun
within the last 3 months). Myocardial infarction less than 6 months
before start of test drug.
- Uncontrolled hypertension despite optimal medical management (per
investigator's assessment).
- Arterial or venous thrombotic or embolic events such as
cerebrovascular accident (including transient ischemic attacks), deep
vein thrombosis or pulmonary embolism within 3 months before the
start of study medication.
- Non-healing wound, ulcer, or bone fracture.
- Active, clinically serious infections (> CTCAE grade 2).
- Patients with seizure disorder requiring medication
- Patients with evidence or history of bleeding diathesis. Any
hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks of start
of study medication.
- Known hypersensitivity to any of the study drugs, study drug classes,
or excipients in the formulation.
- Proteinuria of CTCAE Grade 3 or estimated by urine protein : creatinine
ratio > 3.5 (> 396 mg/mmol)on a random urine sample
- Unresolved toxicity higher than NCI-CTCAE grade 1 attributed to any
prior therapy/procedure excluding alopecia.
- Concurrent diagnosis of pheochromocytoma.
- Pregnant or breast-feeding patients. Women of childbearing potential
must have a pregnancy test performed a maximum of 7 days before start
of treatment, and a negative result must be documented before start of
treatment.
- Substance abuse, medical, psychological or social conditions that may
interfere with the patient's participation in the study or evaluation of the
study results.
- Any illness or medical conditions that are unstable or could jeopardize
the safety of the patients and their compliance in the study.
- Prior treatment with copanlisib
- Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at
baseline will not be eligible.
CMV PCR test is considered positive if the result can be int
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