Biomarker driven treatment for patients less than 65 years with aggressive B-cell lymphoma
- Conditions
- Diffuse large B-cell lymphomaMedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002846-30-DK
- Lead Sponsor
- HUS-The Hospital District of Helsinki and Uusimaa
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 120
•Age ? 18 - < 65 years
•Histologically confirmed CD20+ DLBCL based on revised WHO 2008 Lymphoma Classification [51]. The following subgroups and variants can be included:
oALK-positive large B-cell lymphoma
oIntravascular large B-cell lymphoma
oT-cell rich B-cell lymphoma
oMyc/BCL-2 double hit lymphoma
oFollicular lymphomas grade 3b
oDLBCL with previously undiagnosed concurrent small cell infiltration in bone marrow, lymph node, or extranodal site and lymphomas intermediate between DLBCL and Burkitt’s lymphoma are allowed
oPosttransplantation lymphoma (PTLD), discordant or transformed lymphoma are NOT allowed
•Patients in at least stage II with age adjusted IPI score of 2 or 3:
oStage III /IV and elevated LDH
oStage III/IV and WHO performance status 2 - 3
oStage II and elevated LDH and WHO performance status 2 – 3
•And/or patients with site specific risk factors for CNS recurrence defined as follows
oMore than one extranodal site
oTesticular lymphoma, stage IIE and higher
oParanasal sinus and orbital lymphoma with destruction of bone
oLarge cell lymphoma infiltration of the bone marrow
•Previously untreated, except steroids allowed
•WHO performance status 0-3
•Written informed consent
Biologically high risk group consists of patients with at least one of the following factor
•Myc translocation (FISH)
•Myc/Bcl2 double hits (FISH)
•P53 deletion (FISH)
•Myc+/Bcl2+ (IHC)
•P53+ (ICH)
•CD5+ (IHC)
The biologically low risk group consists of patients without the above listed factors.
Paraffin-embedded tumor tissue must be sent to the central laboratory for determination of biological risk factors
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 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
•Severe cardiac disease: cardiac function grade 3-4, left ventricular ejection fraction <45%
?Impaired bone marrow liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule (Hemoglobin < 9 g/dL, ANC < 1.5 × 109/L, Platelet count < 75 × 109/L, creatinine clearance < 40 mL/min, ALT/AST > 2.5 x ULN, bilirubin >= 1.5 x ULN, INR > 1.5)
•Pregnancy/lactation
•Men and women of reproductive potential not agreeing to use effective contraception during treatment and for 18 months after completion of treatment
•Patients with other severe medical problems, including active infections, cardiac or pulmonary disease, history of PML and with an expected short survival for non-lymphoma reasons
•Known HIV positivity
•Active or chronic hepatitis B virus (HBV) infection (defined as positive HBsAg serology), or active hepatitis C virus (HCV) infection (defined by antibody serology testing). HBsAg, HBcAb, and HCVAb must be tested during screening. Patients who have protective titers of HBsAb along negative HBsAg after vaccination or prior but cured hepatitis B are eligible.
•Vaccination with a live vaccine within one month prior to randomization
•Patients with a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for = 5 years prior to enrollment
•Earlier treatment containing anthracyclins
•Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
•CNS disease as diagnosed by MRI or CSF cytology. Positive CSF flow cytometry below diagnostic threshold level by cytology is allowed
•Transformed lymphoma
•Primary mediastinal B-cell lymphoma
•Pleural or peritoneal fluid that cannot be drained safely
•Hypersensitity to the active substance or any of the other ingredients
•History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
•Patients participating in other clinical studies, unless followed for survival
•Lower urinary tract constriction, which cannot be treated adequately
•Degenerative and toxic encephalopathy
•Neuromuscular disease
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