E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
DIFFUSE LARGE BCELL
LYMPHOMA |
|
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 |
|
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 |
Evaluation of efficacy and safety of [90Y]-ibritumomab tiuxetan, as well as assessment of quality of life |
|
E.2.2 | Secondary objectives of the trial |
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 CHOP from 6-8 to 4. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Histologically confirmed, Ann Arbor stage II, III, or IV DLBCL according to the REAL/WHO
classification (from initial diagnosis made prior to starting CHOP21-R therapy);
2. Central pathology review confirming the DLBCL diagnosis and CD20 positivity, and no
evidence/evidence with an infiltration <25% of DLBCL in bone marrow;
3. The first part of the treatment of DLBCL must have been 4 cycles of standard CHOP21 chemotherapy
(cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 up to a maximum of 2
mg on day 1, and at least 40 mg/m2/day prednisone on Days 1 to 5 every three weeks) in combination
with rituximab (375 mg/m2);
4. Complete remission (CR), unconfirmed complete remission (CRu), partial response, and nonresponder
according to the International Workshop Response Criteria for NHL described by Cheson
et al (18) afterfour cycles of CHOP21-R. 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 CHOP21-
R;
5. Patients 60-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) ᄈ 1.5 x 109/L within 1 week of accrual;
8. Hemoglobin (Hgb) ᄈ 10 g/dL within 1 week of accrual;
9. Platelets. 150 x 109/L within 1 week of accrual.
10. Life expectancy of 3 months or longer
11. Written informed consent obtained according to local guidelines |
|
E.4 | Principal exclusion criteria |
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 CHOP21-R 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. Treatment with investigational drugs less than 4 weeks before the planned Day 1 or nonrecovery from
the toxic effects of such therapy;
14. Surgery less than 4 weeks before the planned Day 1 or nonrecovery from the side effects of such
surgery;
15. 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;
16. Unwillingness or inability to comply with the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate and complete response rate will be the primary endpoints, |
|
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 |