To determine the dose of BI 836826-GemOx and the efficacy of BI 836826-GemOx versus R-GemOx in patients with relapsed/refractory DLBC
- Conditions
- Patients with relapsed/refractory DLBCL (including transformedfolicullar lymphoma) who have been pretreated with an anti-CD20monoclonal antibody (e.g. rituximab) in combination with ananthracycline containing chemotherapy and who are not eligible for, orhave failed autologous stem cell transplant.MedDRA version: 21.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2014-004794-16-IT
- Lead Sponsor
- BOEHRINGER-INGELHEIM ITALIA S.P.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 35
- Age 18 years or older
- Patients with histologically confirmed, relapsed/refractory, diffuse
large B-cell lymphoma (including transformed follicular lymphoma) who
have received an anti-CD20-supplemented, anthracycline-containing
chemotherapy and are not eligible for high dose therapy followed by an
autologous stem cell transplant, or have failed autologous stem cell
transplant Previous allogenic stem cell transplant is allowed if patients
do not require immunosuppressive treatment for at least 8 weeks prior
to enrollment in the trial and have no evidence of active graft-versushost
disease
- Patient has not received anti-lymphoma treatment prior to the first
dose of trial medication: within past 14 days or within time that is
shorter or equal to 5 half-lives of the drug if the last anti-lymphoma
treatment contained an investigational agent
- Screening computer tomography (CT) scan with involvement of 2 or
more clearly demarcated lesions/nodes with a long axis >1.5cm
- Screening [18F] flourodeoxyglucose (FDG)- positron emission tomography (PET) scans must demonstrate positive lesion compatible
with computer tomography (CT) defined anatomical tumor sites
- ECOG performance status 0, 1, 2
- Written signed informed consent consistent with ICH GCP and local
legislation
- Patients must have an acceptable organ function
- Women of childbearing potential must be ready and able to use highly
effective methods of birth control per ICH M3(R2) that result in a low
failure rate of less than 1% per year when used consistently and
correctly. A list of contraception methods meeting these criteria is
provided in the patient information. Male patients having a partner of
childbearing potential must use condoms and ensure their partner is
using a highly effective method of birth control as described above,
during the trial and for at least 12 months after the end of the trial.
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 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 128
- Eligible for curative salvage high dose therapy followed by stem cell
transplant
- Primary central nervous system lymphoma or known Central nervous
system (CNS) involvement
- Prior history of malignancy other than DLBCL except basal cell or
squamous cell carcinoma of the skin, or carcinoma in situ of the uterine
cervix or breast which has been treated with curative therapy. Other
prior malignancies are allowed only if patient has been free of disease
and without treatment other than hormones for at least past three years.
- Refractory to gemcitabine and/or oxaliplatin
- Contraindications for gemcitabine, oxaliplatin and/or rituximab as
judged by the investigator. Hypersensitivity to oxaliplatin
- Unresolved toxicity of CTCAE grade > 1from prior therapy (except
alopecia)
- Significant concurrent medical disease or condition which according to
the investigators judgment would either compromise patient safety or
interfere with the evaluation of the safety of the test drug. e.g.
symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia requiring therapy with the exception of extra systoles of
minor conduction abnormalities
- An infection requiring treatment at the start of the trial medication.
- Hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
infection with positive test results from the virology screening
- Women who are pregnant, nursing, or who plan to become pregnant
while in the trial
- Known alcohol or drug abuse which could potentially interfere with
trial participation according to investigator¿s judgment
- Prior treatment with CD37 antibody
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To establish the maximum tolerated dose (MTD) of BI 836826 in combination with GemOx;Secondary Objective: To evaluate pharmacokinetics of BI 836826 when administered in<br>combination with GemOx;Timepoint(s) of evaluation of this end point: 1) 14 days from first trial medication<br>2) 14 days from first trial medication<br>3) 14 days from first trial medication;Primary end point(s): 1) The number of patients with DLTs in cycle 1<br>2) The MTD of BI 836826 with GemOx is defined as the highest dose<br>studied for which the number of patients with dose-limiting toxicity is<br>17% or less (i.e., 0-1/6 patients) during cycle 1<br>3) Overall response (OR) by central review assessment, i.e. partial treatment arms<br>response (PR) and complete remission (CR) by central review<br>assessment, analyzed by the ORR and compared between the two
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) The secondary endpoint will be pharmacokinetic parameters: AUCt<br>and Cmax of BI 836826 when administered in combination with GemOx<br>2) The CR by central review assessment will be the secondary endpoint,<br>and will be compared between the two treatment arms;Timepoint(s) of evaluation of this end point: 1)up to 32 weeks from first trial medication administration.<br>2)up to 32 weeks from first trial medication administration.