E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
follicular grade I-II
lymphoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
|
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 |
The objectives of this study are to evaluate the efficacy and safety of the Zevalin study
regimen after 4 cycles of FMR. |
|
E.2.2 | Secondary objectives of the trial |
disease-free survival (DFS) and the rate
of complete response will be the secondary endpoint. An additional secondary endpoint will be
health-related quality of life(HRQL) considering that on this way (with introduction of Zevalin) we
reduce the total number of cycles of conventional chemotherapy FM from 6-8 to 4. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
6
Histologically confirmed FL grade I-II according to the REAL/WHO classification (from
initial diagnosis made prior to starting FMR therapy);
2. FLIPI οΎ³ 3; 3
3. Central pathology review confirming the FL grade I-II diagnosis and CD20 positivity, and
no evidence/evidence with an infiltration <25% of FL in bone marrow;
4. The first part of the treatment of FL must have been 4 cycles of standard FM chemotherapy
(fludarabine 25 mg/m2/day on days 1 to 3 and mitoxantrone 10 mg/m2 on day 1) in
combination with rituximab (375 mg/m2); Complete remission (CR), unconfirmed complete
remission (CRu), partial response, and non-responder according to the International
Workshop Response Criteria for NHL described by Cheson et al (13) after four cycles of
FMR. CT scans of the neck, thorax, abdomen, and pelvis and PET total body must have
been performed within 3 weeks after the last dose of the last course of FMR;
5. Patients 18-years-of-age or older at time of accrual;
6. WHO performance status (PS) of 0 to 2 within 1 week of accrual;
7. Absolute neutrophil count (ANC). 1.5 x 109/L within 1 week of accrual;
8. Hemoglobin (Hgb). 10 g/dL within 1 week of accrual;
9. Platelets. 150 x 109/L within 1 week of accrual.
10. Written informed consent obtained according to local guidelines |
|
E.4 | Principal exclusion criteria |
1. Presence of any other malignancy or history of prior malignancy except non-melanoma skin
tumors or stage 0 (in situ) cervical carcinoma;
2. Prior radioimmunotherapy, radiation therapy, or any other NHL therapy;
3. Presence of gastric, central nervous system (CNS), or testicular lymphoma at first diagnosis;
4. Histological transformation of low-grade NHL;
5. Known seropositivity for hepatitis C virus (HCV) or hepatitis B surface antigen (HbsAg);
6. Known history of HIV infection;
7. Abnormal liver function: total bilirubin > 1.5 x ULN or ALT > 2.5 x ULN within 1 week of
accrual;
8. Abnormal renal function: serum creatinine > 2.0 x ULN within 1 week of accrual;
9. Nonrecovery from the toxic effects of FMR therapy;
10. Known hypersensitivity to murine or chimeric antibodies or proteins;
11. G-CSF or GM-CSF therapy within two weeks (or four weeks if pegylated) prior to screening
laboratory sampling;
12. Concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, congestive
heart failure, myocardial infarction within 6 months of study, unstable anduncontrolled
hypertension, chronic renal disease, or active uncontrolled infection) which could compromise
participation in the study;
13. Male and female patients of child-bearing potential unwilling to practice effective contraception
during the study and unwilling or unable to continue contraception for 12 months after their last
dose of study treatment;
14. Female patients who are pregnant or are currently breastfeeding;
15. Treatment with investigational drugs less than 4 weeks before the planned Day 1 or
nonrecovery from the toxic effects of such therapy;
16. Surgery less than 4 weeks before the planned Day 1 or nonrecovery from the side effects of
such surgery;
17. Concurrent corticosteroid use for any reason except as premedication in case of known or
suspected allergies to contrast media or as premedication for potential side effects of rituximab
treatment;
18. Unwillingness or inability to comply with the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS) will be the primary endpoint, |
|
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 | No |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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 | No |
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.8.5 | 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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |