Study of a new drug combination for the treatment of Non Hodgkin's Lymphoma

Phase 1

• Conditions: Indolent B-cell Non-Hodgkin’s Lymphoma; MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-004177-17-PL
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-03-24
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 346

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the
following criteria:
1. Small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma,
marginal
zone lymphoma, and follicular lymphoma; grades 1, 2 and 3A, defined
according to World Health Organization guidelines. Subjects with a
diagnosis
of SLL who have a peripheral blood monoclonal B lymphocyte count of
=5,000/µL are considered to have CLL and are not eligible for this study.
• Tumor verified to be CD20+ positive from a previous or current tissue
biopsy.
•CT imaging in screening phase (based on local evaluation) showing 2 or
more clearly demarcated lesions/nodes with a long axis >1.5 cm and
short axis = 1.0 cm or 1 clearly demarcated lesion/node with a long axis >2.0 cm and short axis =1.0 cm (Section 6.2.5 of Study Protocol). CT imaging performed at screening as baseline image.
2. Indolent B-cell NHL with failure to achieve at least a partial response
lasting 6 months beyond the end of treatment with rituximab or a rituximabcontaining regimen (See Section 6.2.5.4– Section 6.2.5.5 of study protocol for details on response criteria), i.e.:
•Stable disease (SD) after rituximab or a rituximab-containing regimen
(imaging will support this finding. NOTE: in cases of SD after rituximab
monotherapy as induction treatment, the minimum time to confirm SD
by imaging is 60 days from start of first rituximab infusion) or,
• Disease progression during or within 6 months of treatment with
rituximab or a rituximab-containing regimen. Imaging must support this
finding and will be done = 6 months after the last infusion of rituximab.
Note: Subjects must have received a minimum of 4 rituximab infusions
as monotherapy or 3 infusions as part of rituximab-containing
combination regimens
3. ECOG Performance Status of 0, 1, or 2
4. Age = 18 years
5. Life expectancy of at least 6 months
6. Signed written informed consent prior to performing any studyspecific procedures
French subjects: In France, a subject will be eligible for inclusion in this
study only if either affiliated to or a beneficiary of a social security category
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 137
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion Criteria

Subjects meeting any of the following criteria will not be enrolled in the
study:
1. Grade 3b FL or evidence that the indolent lymphoma has transformed to aggressive lymphoma as verified by biopsy confirmation
2. Previous autologous stem cell transplant in the last 6 months or
previous allogeneic stem cell transplant at any time.
3. High dose steroids = 25 mg prednisolone/day (or equivalent) for 7
consecutive days, given as concomitant medication, within 3 months prior to randomization. No more than 10 mg prednisone daily at the time of randomization
4. Prior bendamustine treatment within 1 year of randomization not
resulting in a CR or PR for at least 6 months
5. Prior use of any monoclonal antibody (other than anti-CD20) within 3
months prior to randomization
6. Known central nervous system (CNS) involvement by indolent
lymphoma
7. Other past or current malignancy. Subjects who have been free of
malignancy for at least 5 years, or have a history of definitively treated nonmelanoma skin cancer, or successfully treated in situ carcinoma, are eligible*
8. Chronic or current active infectious disease requiring systemic
antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active Hepatitis C
9. Clinically significant cardiac disease as judged by the investigator
including unstable angina, acute myocardial infarction within 6 months of randomization, congestive heart failure, and arrhythmia requiring therapy
10. History of significant cerebrovascular disease or event with
significant symptoms or sequelae
11. Significant concurrent, uncontrolled medical condition that in the
opinion of the investigator or GSK medical monitor contraindicates
participation this study
12. Positive serology for Hepatitis B (HB) defined as a positive test for
Hepatitis B surface antigen (HbsAg). In addition, if negative for HBsAg but Hepatits B core antibody (HBcAb) positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded
? Consult with a physician experienced in care and management of
subjects with Hepatitis B to manage/treat subjects who are anti-HBc positive
? If HBV DNA is negative, subject may be included but must undergo HBV DNA monitoring (see Section 6.5.7.1 of study protocol). Prophylactic antiviral therapy may be initiated at the discretion of the investigator
13. Current active liver or biliary disease (subjects with Gilbert's
syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible)
14. Known human immunodeficiency virus (HIV) positive
15. Screening laboratory values:
? platelets < 100 x 109/L (unless due to indolent lymphoma involvement
of the bone marrow)
? neutrophils < 1.5 x 1

Study & Design

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