E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated CD20-positive lymphoproliferative disorder (PTLD) following solid organ transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Previously untreated CD20-positive lymphoproliferative disorder (PTLD) following solid organ transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051358 |
E.1.2 | Term | Post transplant lymphoproliferative disorder |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 determine the safety and the efficacy of first-line risk stratified* sequential treatment with 4 weekly courses of rituximab SC** followed by
• 4 courses of rituximab SC monotherapy ever 3 weeks in low-risk patients, • 4 cycles of rituximab SC plus CHOP (+GCSF) ever 3 weeks in high-risk patients, • 6 alternating cycles of rituximab SC plus CHOP+GCSF or DHAOx+GCSF applied ever 3 weeks in very high-risk patients
diagnosed with CD20-positive post-transplant lympho¬prolifera¬tive disorder following solid organ transplantation.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• CD20-positive PTLD with or without EBV association, confirmed after biopsy or resection of tumor • Measurable disease of > 2 cm in diameter and/or bone marrow involvement • Patients having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or a combination of the organ transplantations mentioned • ECOG ≤ 2 • Clinically insufficient response to an upfront reduction of immunosuppression with or without antiviral therapy • Age at least 18 years • Not legally incapacitated • Written informed consent from the trial subject has been obtained
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E.4 | Principal exclusion criteria |
• Complete surgical extirpation of the tumor or irradiation of residual tumor masses • Missing data for IPI stratification • Upfront treatment with rituximab or chemotherapy • Known allergic reactions against foreign proteins • Concomitant diseases, which exclude the administration of therapy as outlined by the study protocol • Meningeal and CNS involvement • Known to be HIV-positive • Pregnant women and nursing mothers • Failure to use highly-effective contraceptive methods • Persons held in an institution by legal or official order • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator • Life expectancy less than 6 weeks
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end point: • Event free survival (EFS) of low-risk patients in the intention to treat population defined as time from start of treatment to event with following definitions for low-risk and event:
1. Low-risk: all patients in complete remission at interim staging, i.e. 4 weeks after the four weekly courses of rituximab SC monotherapy all patients in partial remission at interim staging with an initial international prognostic index (IPI) of 0,1 or 2 all patients in partial remission at interim staging with a negative PET scan*
2. Events: any grade III or IV infection during the treatment period treatment discontinuation for any reason disease progression at any time death (any cause)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary end points: • Overall survival, time to progression, progression free survival, response and overall response at interim staging, response and overall response after full treatment, duration of response, treatment related mortality in the ITT and PP population • Secondary end points will be analyzed in the total trial cohort and by treatment group Other variables: • Frequency of grade III and IV leucocytopenia and grade III and IV infections by treatment group
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Response and overall response at interim staging: day 50 Response and overall response after full treatment: day 143/187 depending on treatment arm Treatment-related mortality: 3 months Overall survival, time to progression, progression free survival, duration of response: 2 years
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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 | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 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 | 21 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |