Ofatumumab for the treatment of lymphoma
- Conditions
- Diffuse Large B-Cell Lymphoma (DLBCL) and grade 3b follicularlymphomaMedDRA version: 14.1Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2009-009256-20-PL
- Lead Sponsor
- GlaxoSmithKline Research and Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 380
1. CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original
diagnosis. If an evaluable biopsy or fine needle aspiration (FNA) is
performed prior to enrolment to the study it must confirm CD20 positive
DLBCL or grade 3b FL. Note: If evidence
emerges that the binding of the immunohistochemical antibody to CD20
can be blocked by rituximab, demonstration of CD20 positivity in the
repeat biopsy/FNA will not be required.
2. Refractory to, or relapsed following, first-line treatment with
rituximab concurrently with anthracycline- or anthracenedione-based
chemotherapy.
Relapse is defined as:
• Biopsy (preferred) or FNA confirmed DLBCL or grade 3b FL after a
complete response (CR) or unconfirmed complete response (CRu).
However, for subjects relapsing during first-line treatment, biopsy/FNA
reconfirmation of the lymphoma is recommended but not mandatory.
Subjects must have received rituximab concurrently with at least 6
cycles of chemotherapy. However, subjects with stage I/II disease will
be eligible if
they have received rituximab concurrently with at least 3 cycles of
chemotherapy and definitive involved-field radiation therapy.
Refractory disease must fulfill one of the following:
• continuing partial response (PR) from termination of first-line
treatment. It is strongly recommended the lymphoma be reconfirmed by
biopsy (preferred) or FNA, however, if these procedures are deemed to
be inappropriate, then HOVON may determine eligibility following review
of the imaging results and disease history.
Subjects must have received rituximab concurrently with at least 6
cycles of chemotherapy. However, subjects with stage I/II disease will
be eligible if they have received rituximab concurrently with at least 3
cycles of chemotherapy and definitive involved-field radiation therapy.
• continuing stable disease (SD) from termination of first-line treatment.
Reconfirmation of the lymphoma by biopsy (preferred) or FNA is
recommended but not mandatory.
Subjects must have received rituximab concurrently with at least 3
cycles of chemotherapy.
• progressive disease (PD). Biopsy or FNA reconfirmation of the
lymphoma is recommended but not mandatory.
3. Baseline FDG-PET scans must demonstrate positive lesions compatible
with CT defined anatomical tumor sites.
4. CT scan showing at least:
• 2 or more clearly demarcated lesions/nodes with a long axis >1.5cm
and short axis =1.0cm
OR
• 1 clearly demarcated lesion/node with a long axis >2.0cm and short
axis =1.0cm.
5. Age =18
6. ECOG performance status 0, 1, or 2.
7. Eligible for high dose chemotherapy and ASCT.
8. Resolution of toxicities from first-line therapy to a grade that in the
opinion of the
investigator does not contraindicate study participation.*
9. Signed written informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Any previous cancer therapy for the lymphoma, with the exception of:
• First-line treatment with rituximab and an anthracycline- or
anthracenedionebased chemotherapy.
• Monotherapy rituximab, dosed prior to first-line rituximab combined with chemotherapy, or as maintenance therapy.
• Radiotherapy as part of the first-line treatment plan.
• Radiotherapy to a limited field at a maximum dose of =10Gy to control lifethreatening symptoms.
• Prophylactic testicular radiotherapy for testicular lymphoma.
• Intrathecal chemotherapy for the prophylaxis of CNS disease.
2. Received any of the following treatments within two weeks prior to start of study therapy (unless otherwise stated):
• Anti-cancer cytotoxics (e.g. alkylating agents, anti-metabolites, purine analogues)
• Radiotherapy unless it is to a limited field at a maximum dose of = 10Gy to control life-threatening symptoms.
3. Treatment with any known non-marketed drug substance or
experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study unless in the opinion of the investigator it does not contraindicate participation in this study.
4. Planned post-randomisation glucocorticoid therapy, unless
• specified by the protocol
• administered in doses =1mg/kg/day prednisolone (or equivalent dose of other glucocorticoid-refer to the SPM for glucocorticoid equivalent doses)
• administered as inhalation therapy for mild COPD or asthma.
5. History of significant cerebrovascular disease or event with significant symptoms or sequelae, unless in the opinion of the investigator it does not contraindicate participation in the study.
6. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomisation, congestive heart failure (NYHA III-IV), a current LVEF of <40%, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities, unless in the opinion of the investigator it does not contraindicate participation in the study.*
7. Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation in this study.
8. Known lymphoma involvement of the CNS.
9. Known or suspected hypersensitivity to study treatments that in the opinion of the investigator contraindicates their participation.
10. Known HIV positivity.
11. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
12. Active hepatitis C infection.
13. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and
tuberculosis.
14. Other past or current malignancy within 2 years prior to
randomization unless in the opinion of the investigator it does not contraindicate participation in the study.
Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer, or
successfully treated in situ carcinoma, are eligible.
15. Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
16. Screening laboratory values:
• plat
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