A Randomised, Phase IIb Placebo-controlled Study of R-ICE Chemotherapy (Rituximab, Ifosfamide, Carboplatin, and Etoposide) with and without SGN-40 (anti-CD40 humanized monoclonal antibody) for Second-line Treatment of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) - SeaGen MARINER trial
- Conditions
- Diffuse Large B-cell LymphomaMedDRA version: 9.1Level: LLTClassification code 10012818Term: Diffuse large B-cell lymphoma
- Registration Number
- EUCTR2007-002917-38-BE
- Lead Sponsor
- Seattle Genetics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 224
Patients must meet ALL of the following inclusion criteria to be eligible for inclusion into the study:
1. Patient has pathologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), including both de novo and transformed DLBCL and follicular lymphoma, Grade 3b (FL3b).38
a. Local pathology review is acceptable for determining eligibility.
b. Prior therapy for indolent lymphoma is not allowed.
c. For patients who have achieved a CR to first-line therapy, a repeat biopsy since relapse for confirmation of disease is required unless all of the following conditions are met:
– Relapse has occurred within 1 year of completing first-line therapy.
– In the investigator’s opinion, the CT and PET imaging and clinical presentation are consistent with relapsed DLBCL or FL3b.
– It is medically unsafe or infeasible to perform a biopsy due to the anatomic location of the tumor(s).
– The site has confirmed that there is adequate tissue from the initial diagnostic biopsy for central review to confirm diagnosis and perform all immunohistochemical and pharmacogenomic studies.
2. Patient has received at least four cycles of first-line therapy with R-CHOP or equivalent first-line therapy including rituximab, cyclophosphamide, anthracycline or anthracenedione, and steroid with or without additional chemotherapy agent(s). For patients who achieve CR with first-line therapy, maintenance therapy prior to relapse is allowed.
3. Patient achieved a response of stable disease, partial response, or complete response following the last cycle of R-CHOP.
4. Patient currently has at least one site of measurable disease meeting both of the following criteria:
- Bidimensional measurement with longest axis greater than or equal to 1.5 cm by radiographic imaging.
- Positive FDG-PET scan at baseline.
Local imaging review is acceptable for determining eligibility.
5. A fresh or archived tumor specimen is available for central review to confirm diagnosis (see Section 9.1.1).
6. Patient has completed first-line therapy at least four weeks prior to the date of randomization.
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
8. Patient is at least 18 years old and no more than 75 years old.
9. Patient has the following required baseline laboratory data (eligibility can be based on local lab results):
- Platelet count greater than or equal to 75,000/mm3.
- Absolute neutrophil count (ANC) greater than or equal to 1,000/mm3 (may be maintained by growth factors).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times upper limit of normal (ULN).
- Total serum bilirubin level less than or equal to 1.5 times ULN.
- Serum creatinine less than or equal to 1.5 times ULN.
10. If a female of childbearing potential, the patient has a negative serum or urine pregnancy test result (sensitivity at least 50 mIU/mL) within three days prior to the first dose of Investigational Drug or on Day -2, prior to first dose. (Females of non-childbearing potential are those who are postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy)
11. If female of childbearing potential or a male patient, patient agrees to use an effective contraceptive method from the time of informed consent, during the course of the study, and for 6 months following the last dose of Investigational Drug.
12. Patient is available for periodic blood sampling, study-related assessme
1. Patient has a history or clinical evidence of leptomeningeal or central nervous system (CNS) lymphoma.
2. Patient has received any therapy for relapsed or progressive disease except for local radiation, steroids, or single-agent rituximab (less than or equal to four infusions).
3. Patient has a documented history of a cerebral vascular event (stroke or transient ischemic attack) or myocardial infarction within six months of screening.
4. Patient has received a hematopoietic stem cell transplant.
5. Patient has been previously treated with an anti-CD40 mAb or any therapeutic radiolabeled antibody.
6. Patient has had major surgery within four weeks prior to randomization.
7. Patient has a known hypersensitivity or anaphylactic reaction to any component of the planned study treatment.
8. Patient has evidence of another invasive primary malignancy anytime in the 12 months prior to screening.
9. Patient has had any systemic viral, bacterial, or fungal infection requiring IV antibiotics within four weeks prior to planned date of randomization.
10. Patient has a known positive test for human immunodeficiency virus (HIV), hepatitis B (by surface antigen expression), or hepatitis C infection.
11. Patient is on systemic steroids exceeding 20 mg/day prednisone or equivalent during any of the seven days prior to randomization.
12. Patient is taking any other systemic immunosuppressive medication during the 14 days immediately prior to randomization (e.g., cyclosporine, azathioprine, mycophenylate mofetil).
13. Patient is pregnant or breastfeeding.
14. Patient has any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment or subsequent SCT.
15. Patient has been diagnosed with dementia or has altered mental status that would preclude the understanding and/or rendering of informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To estimate the complete response (CR) rate of patients receiving R-ICE in combination with SGN-40 versus R-ICE in combination with placebo in patients with DLBCL after receiving R-CHOP or equivalent first-line therapy.;Secondary Objective: To assess the safety and tolerability of a combined therapy of R-ICE in combination with SGN-40 versus R-ICE in combination with placebo in patients with DLBCL after receiving R-CHOP or equivalent first-line therapy.;Primary end point(s): Complete response (CR) as assessed by CT and PET scans and revised response criteria for malignant lymphoma at completion of study therapy prior to transplant.
- Secondary Outcome Measures
Name Time Method