E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse large B-cell Non-Hodgkin's lymphoma (DLBCL) |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate efficacy and safety of inotuzumab ozogamicin in combination with rituximab when used as induction therapy prior to consolidation with HD chemo and aSCT in subjects with relapsed/refractory CD22-positive DLBCL. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the ability of inotuzumab ozogamicin plus rituximab to allow for successful PBSC mobilization and collection, as measured by mobilization-adjusted ORR and the rate of successful PBSC collections. To evaluate the efficacy of inotuzumab ozogamicin plus rituximab for use as induction therapy prior to consolidation with HD chemo and aSCT, as measured by transplantation rate and event free survival (EFS). To evaluate the population pharmacokinetic (PK) profile of inotuzumab ozogamicin. To evaluate the toxicities of inotuzumab ozogamicin plus rituximab. To evaluate the efficacy of inotuzumab ozogamicin plus rituximab as measured by PFS, CR and OS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with a diagnosis of CD20 and CD22-positive DLBCL who have relapsed after achieving a complete or partial response or whose best response was stable disease after 1 or 2 prior regimens; one prior chemotherapy regimen must have contained anthracyclines (with or without rituximab) and one regimen must have included rituximab in combination with chemotherapy. Disease status at the time of first dosing requires at least one of the following characteristics: a. Relapsed or disease progression occurring < 12 months after start of the prior therapy. b. Secondary International Prognostic Index (sIPI) score > 1. 2. Eligible for aSCT. 3. Male and female subjects aged 18 years or older. 4. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/μL) and platelets ≥ 100 x 109/L (100,000/μL). 5. Total bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate and alanine aminotransferase (AST, ALT) ≤ 2.5 x ULN. 6. At least 1 measurable disease lesion that is ≥ 1.0 cm in 2 perpendicular dimensions, with the sum of the product diameters > 2.25 cm2 by computed tomography (CT) or magnetic resonance imaging (MRI). 7. Serum creatinine ≤ 2.0 x ULN and urine protein/creatinine ratio ≤0.5. 8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 9. Life expectancy ≥3 months. 10. Negative serum pregnancy test within 1 week before first treatment if the subject is a woman of childbearing potential. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. 11. All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study, including up to 18 months after the last dose of induction therapy test article. A subject is biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives. |
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E.4 | Principal exclusion criteria |
1. Prior allogeneic hematopoietic stem cell transplant (HSCT). 2. Prior autologous transplant ≤6 months before first dose of test article. 3. Prior treatment with anti-CD22 antibodies; or previous radio-immunotherapy ≤6 months before first dose of test article. 4. Subjects whose disease progressed while receiving rituximab in combination with chemotherapy. 5. History of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS). 6. Intolerance to rituximab or history of severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies. 7. Known systemic vasculitides. 8. Immunocompromised subjects, including current or chronic hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV). 9. Evidence of serious active infection (eg, requiring an intravenous [IV] antibiotic or antiviral agent). 10. Major surgery, not related to debulking surgical procedures, ≤28 days before first dose of test article. 11. Chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational drugs/devices ≤28 days before first dose of test article. Subjects receiving high doses of corticosteroids must have been tapered to a stable and acceptable dose at least 28 days before the first dose of inotuzumab ozogamicin 12. Pregnant or breastfeeding women. 13. Symptomatic central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected. 14. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition). 15. Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for ≥2 years. 16. Primary effusion lymphoma. 17. Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 50%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure. 18. Previous myocardial infarction or pulmonary hypertension ≤6 months before first dose of test article. 19. History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse. 20. Administration of a live vaccine ≤6 weeks before first dose of test article. 21. Any major illness/condition or abnormal laboratory finding that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall (objective) response rate (ORR): Complete Reponse + partial response after 3 cycles of inotuzumab ozogamicin plus rituximab therapy. |
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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 | 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 | 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) | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | No |
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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Last follow-up visit of the last subject enrolled. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |