Clinical trial with Copanlisib in combination with Rituximab and Bendamustine in patients with Relapsed-Refractory Diffuse Large B-cell Lymphoma

Phase 1

• Conditions: Patients with Relapsed-Refractory Diffuse Large B-cell Lymphoma; MedDRA version: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-004898-63-IT
• Lead Sponsor: FONDAZIONE ITALIANA LINFOMI ONLUS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-21
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 81

Inclusion Criteria

1.Histologically confirmed diagnosis of DLBCL (de-novo DLBCL or DLBCL transformed by indolent lymphoma; high grade double hit lymphoma can be included); new biopsy at relapse time is recommended, but not mandatory.
2.Patients must have relapsed (recurrence after complete response or presented progression after partial response) or refractory after at least = 1 (but < 4) prior lines of therapy, including rituximab-based immunochemotherapy.
A previous regimen is defined as one of the following: at least 2 months of single-agent therapy; at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy.
3.Patients must not be eligible to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or relapsed after that.
4.Patients must not be eligible to CAR T-cell therapy or relapsed after that.
5.Patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the 2014 Lugano criteria.
6.Male or female patient = 18 years of age.
7.Eastern Cooperative Oncology Group (ECOG) performance status = 2 if not related to lymphoma disease.
8.Ann Arbor stage II-IV disease.
9.Life expectancy of at least 3 months.
10.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 6 months after last administration of bendamustine or copanlisib or 12 months after last rituximab dose.
11.Adequate liver, renal and bone marrow function, assessed by baseline laboratory values as assessed within 7 days before starting study treatment; as indicated by the protocol
12.Left ventricular ejection fraction = 45%.
13.Ability to understand and willingness to sign written informed consent. Signed informed consent must be obtained before any study specific procedure.
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 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1.Primary mediastinal B-cell Lymphoma (PMBCL)
2.High grade B-lymphoma NOS (other morphology)
3.Known lymphomatous involvement of the central nervous system
4.Congestive heart failure > New York Heart Association (NYHA) class 2
5.Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
6.Myocardial infarction less than 6 months before start of test drug
7.Uncontrolled arterial hypertension despite optimal medical management
8.HbA1c> 8.5%
9.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
10.Non-healing wound, ulcer, or bone fracture
11.Active, clinically serious infections > CTCAE Grade 2
12.History of, or current autoimmune disease
13.Known history of Human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations.
14.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, these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA
15.CMV PCR positive at baseline
16.Previous or concurrent history of malignancies other than DLBCL 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
17.Patients with seizure disorder requiring medication
18.Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study medication
19.Proteinuria of = CTCAE Grade 3 as assessed by a 24h protein quantification or estimated by urine protein: creatinine ratio > 3.5 on a random urine sample
20.History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
21.Concurrent diagnosis of pheochromocytoma
22.Pregnant or breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
23.Unresolved toxicity higher than CTCAE Grade 1 attributed to any prior therapy/procedure, excluding alopecia
24.Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation
25.Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results
26. Any illness or medical conditions that are unstable or could jeopardize the safety of patients and their compliance in the study e.g., uncontrolled diabetes, uncontrolled dyslipidemia, etc.)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified