E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse Large B-cell Lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012818 |
E.1.2 | Term | Diffuse large B-cell lymphoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 assessments, and management of toxicity at the treating institution. 13. Patient or their legally authorized representative understands and voluntarily signs the written informed consent prior to any study-specific procedures. A copy of the signed informed consent form will be retained by the treating institution. |
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E.4 | Principal exclusion criteria |
Unless a signed medical exception has been documented and approved by the Medical Monitor prior to randomization, patients must be negative for all of the following exclusion criteria to be eligible for the study: 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. |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |