E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory, Follicular Non-Hodgkin’s Lymphoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029627 |
E.1.2 | Term | Non-Hodgkin's lymphoma unspecified histology intermediate grade refractory |
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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 compare the clinical benefit of galiximab in combination with rituximab with that of rituximab monotherapy for the treatment of subjects with relapsed or refractory, follicular NHL.
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E.2.2 | Secondary objectives of the trial |
· To further characterize the safety profile of galiximab in combination with rituximab. · To further characterize the pharmacokinetics (PK) of 4 infusions of galiximab in combination with rituximab.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be considered for registration and randomization into this study, subjects must satisfy all of the following criteria: 1. Must give written informed consent and any authorizations as required by local law 2. Aged ≥18 years old at the time of informed consent 3. Histologically confirmed follicular Grade 1-3a NHL. If slides and/or tissue blocks from the most recent lymph biopsy are not available for Central Pathology Review, a repeat lymph node biopsy is required prior to enrollment. If there is any clinical evidence suggesting transformation (e.g. elevated LDH >2× upper limit of normal), a biopsy is required within 6 months prior to enrollment. Subjects with evidence of histologic transformation on a repeat biopsy are excluded from this study. 4. Relapsed or progressive disease after at least 1 prior chemotherapy requiring treatment as determined by one of the following: - Documented disease progression by CT scan using the International Workshop Response Criteria (IWRC) as described in protocol Appendix C - The presence of B symptoms - Bulky disease (at least 1 lesion >5 cm) - Laboratory abnormalities (cytopenias) - Presence of masses which are causing ongoing clinical symptoms 5. Bidimensionally measurable disease with at least 1 lesion ≥2.0 cm in a single dimension 6. Hematologic, hepatic, and renal function parameters satisfying the following: - Bilirubin ≤2.0 mg/dL - AST (SGOT) ≤2 x upper limit of normal (ULN) and ALT (SGPT) ≤ 2 x ULN - Serum creatinine ≤ 2.0 mg/dL - Hemoglobin ≥ 8.0 g/dL - Absolute neutrophil count ≥ 1500 cells/mm3 - Platelet count ≥ 75,000 plts/mm3 7. WHO Performance Status ≤ 2 8. Recovered fully from any significant toxicity associated with prior surgery, radiation treatments, chemotherapy, biological therapy, autologous bone marrow or stem cell transplant, or investigational drugs 9. Expected survival of ≥ 3 months 10. Subjects of reproductive potential must agree to follow accepted birth control methods during treatment and for 12 months after completion of treatment.
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E.4 | Principal exclusion criteria |
Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of randomization: 1. Follicular lymphoma Grade 3b 2. Previous exposure to galiximab or any anti-CD80 antibody 3. Known hypersensitivity to murine proteins 4. Rituximab refractory or refractory to anti-CD20 radioimmunotherapy (no response to prior rituximab or prior rituximab-containing regimen, or a response with a TTP of less than 6 months) 5. Cancer radiotherapy, biological therapy, or chemotherapy within 3 weeks prior to Study Day 1 (6 weeks if nitrosourea or mitomycin-C) 6. Prior lymphoma vaccine therapy within 12 months prior to Study Day 1 7. Chronic or intermittent corticosteroids for inflammatory or autoimmune disorders within 3 weeks prior to Study Day 1 8. Prior antibody therapy for lymphoma (including radioimmunotherapy) within 6 months prior to Study Day 1 9. Autologous bone marrow or stem cell transplant within 6 months prior to Study Day 1 10. Prior allogeneic transplant 11. Transfusion-dependent subjects 12. Known history of hepatitis or hepatic disease. (Although testing for hepatitis B is not mandatory, this should be considered for all subjects considered at high risk for hepatitis B infection and in endemic areas. Subjects with any serological evidence of current or past hepatitis B exposure should be excluded unless the serological findings are clearly due to vaccination.) 13. Presence of chronic lymphocytic leukemia (CLL), marginal zone lymphoma, mucosa-associated lymphoid tissue (MALT) 14. Presence of central nervous system (CNS) lymphoma 15. Known history of HIV infection or AIDS 16. Prior diagnosis of aggressive NHL or mantle-cell lymphoma 17. Histologic transformation 18. Presence of pleural or peritoneal effusion with positive cytology for lymphoma 19. Another primary malignancy requiring active treatment (except hormonal therapy) 20. Serious nonmalignant disease (e.g., congestive heart failure, hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions, which would compromise protocol objectives in the opinion of the Investigator and/or the Sponsor 21. New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to Study Day 1 22. Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1 23. History of alcoholism or substance abuse within the 2 years prior to Study Day 1 24. Pregnant or currently breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study endpoint is Progression-Free Survival (PFS). |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Combination of galiximab with rituximab versus placebo and rituximab |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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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The purpose of the interim analyses will be to terminate the study early if superiority/futility of the galiximab in combination with rituximab group is demonstrated for progression free survival, the primary efficacy endpoint. A total of 4 analyses (3 interim and 1 final) are planned; however, the first interim analysis will be exclusively for futility with no stopping for efficacy. An Independent Data Monitoring Committee will monitor safety and efficacy at each interim analysis. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |