| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061275 |
| E.1.2 | Term | Mantle 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 |
| To evaluate the efficacy of lenalidomide as maintenance therapy to prolong progression-free survival (PFS) after completion of first-line high-dose chemotherapy additioned with rituximab and followed by ASCT in adult patients with MCL who have achieved complete response (CR) or partial response (PR). PFS is defined according to Cheson et al (JCO, 2007) as the time from randomisation until lymphoma progression or death as a result of any cause. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate:
1) overall survival;
2) disease and event-free survival;
3) safety of lenalidomide as maintenance therapy after completion of first-line highdose chemotherapy additioned with rituximab and followed by ASCT in adult patients with MCL who have achieved CR or PR;
4) efficacy and safety of a simplified R-HDS regimen followed by HDC+ASCT as consolidation after R-CHOP induction;
5) overall clinical response at the end of treatment and at the end of study;
6) activity of lenalidomide maintenance on minimal residual disease assessed in terms of: rate of conversion to molecular remission, rate of molecular relapse, disease kinetics by real time PCR in the bone marrow (BM) and peripheral blood (PB).
7) prognostic impact of molecular response, molecular relapse and disease kinetics by real time PCR on PFS
8) quality of life
9) cost-effectiveness of the maintenance with lenalidomide vs observation (Italian centres only). |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FULL TITLE: Biological characterization of patients enrolled in the IIL-MCL-0208 randomized trial: An ancilliary observatiional study.
VERSION AND DATE: version 1 dated March 2009
OBJECTIVES: To investigate the biology of MCL lymphoma patients enrolled in the IIL-MCL-0208 using a number of biological tools with the following final aims: 1) to better characterize the pathogenesis of MCL; 2) to identify prognostic subgroups; 3) to identify markers of specific treatment responsiveness or increased risk of toxicity; 4) to identify and monitor treatment-related damage to the haematopoietic compartment. |
|
| E.3 | Principal inclusion criteria |
1. Any male or female adult with newly diagnosed mantle cell lymphoma according to the WHO criteria.
2. Biopsy-proven mantle cell non-Hodgkin’s lymphoma, including evidence of cyclin D1
overexpression or the translocation t(11;14)(q13;q32) by FISH or RT-PCR. In subjects
whose tumors are negative for the cyclin D1, evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable.
3. Age>18 years and <60 with ECOG performance status 0-3, or an age from 60 to 65 years with an ECOG performance status 0-2, except when PS impairment is related to NHL.
4. Advanced stage (Stage III and IV according to Ann Arbor and stage II with bulky disease defined as a mass > 5 cm or B symptoms).
5. Measurable disease (two diameters) in at least one site. Osteoblastic bone lesions, ascites and pleural effusion are not considered measurable disease.
6. Written informed consent prior to any study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
7. Be willing and able to comply with the protocol for the duration of the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
• Female subjects of childbearing potential must: 1) Understand that the study medication could have an expected teratogenic risk; 2) Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhea; 3) Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks and every 4 weeks including 4
weeks after the end of study treatment, except in the case of confirmed tubal
sterilization.
• Male subjects must agree: 1) to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception; 2) Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
|
|
| E.4 | Principal exclusion criteria |
1. Non-Hodgkin’s lymphoma subtypes other than MCL
2. Cytological variant with small cells with round nuclei mimicking CLL, which is
frequently recognized in patients with a leukemic and splenomegaly presentation
without or with minimal involvement of lymph nodes and has an indolent clinical
course.
3. History of malignancy other than squamous cell carcinoma, basal cell carcinoma of
the skin or carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental
histological finding of prostate cancer (TNM stage of T1a or T1b) within the last 3 years.
4. Major surgery, other than diagnostic surgery, within the last 4 weeks.
5. Evidence of CNS involvement, patients with an history of uncontrolled seizures,
central nervous system disorders or psychiatric disability considered by the
Investigator to be clinically significant and adversely affecting compliance to study
drugs. If clinically indicated, lumbar puncture, and MRI should be performed during the screening process.
6. Clinically significant cardiac disease cardiac (VEF <45%) (e.g. congestive heart
failure, symptomatic coronary artery disease and cardiac arrhythmias not well
controlled with medication) or myocardial infarction within the last 6 months (New
York Heart Association Class III or IV heart disease) and marked impairment of
pulmonary function (pulmonary diffusing capacity <50%).
7. Unacceptable hematologic values in the week prior to the start of study: hemoglobin <9 g/dL, WBC <3x109/L, platelets <60x109/L, absolute neutrophil count
(ANC)<1.5x109/L (unless cytopenia is secondary to bone marrow involvement or
autoimmune cytopenia related to lymphoma).
8. Abnormal liver function tests, not disease related, within one week prior to study
start above any of the values listed: serum bilirubin > 2 mg/dL, ALT or AST >3.
times the upper normal value; alkaline phosphatase>2.5 times the upper normal
value (unless these abnormalities are due to liver involvement of lymphoma).
9. Abnormal renal function (serum creatinine >2.0 mg/dL), unless it is disease related
10. Patients with active opportunistic infections.
11. Known seropositivity for or active viral infection with human immunodeficiency
virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
seropositive because of hepatitis B virus vaccination are eligible. Patients who are
seronegative for HbsAg, but with HBcAb positive serology, will not be excluded from the study and be given Lamivudine (100 mg die) as prophylaxis starting one
week before chemotherapy. HbsAg and AST/ALT and HBVDNAifavailable, will be
monitored every three weeks. Lamivudine therapy should be continued for one year
after autotransplant. In the group of patients treated with Lenalidomide maintenance therapy after the first year of Lamivudine treatment, AST/ALT and HbsAg will be
monitored every four weeks during the second year if HBVDNA is not available.
12. Pregnant or lactating females. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 2years -Progression-free survival (PFS) |
|
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 |
|
| 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 | 50 |
| 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 |
|
| 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
| |
| 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 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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