| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10060707 |
| E.1.2 | Term | MALT lymphoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 clinical potential of Rituximab plus Lenalidomide to induce objective/histologic responses in patients with MALT lymphoma |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety of Rituximab plus Lenalidomide in this patient population |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For inclusion in the study, all of the following inclusion criteria must be fulfilled:
•Patient understands and voluntarily signs the informed consent prior to any study
related assessments/procedures
•Male or female ≥ 18 years of age
•Histologically verified diagnosis of MALT lymphoma of any localization
•Measurable disease upon diagnosis or first or greater relapse after local therapy
(including gastrectomy or any type of surgery or radiation), prior chemotherapy or HP-eradication. In addition, also patients with gastric MALT-lymphoma judged refractory to HP-eradication by a minimum follow-up of 12 months after successful HP-eradication will be included in the study. Patients with gastric MALT lymphoma and no evidence of HP-infection (as judged by histology and ultimately serology) may be enrolled immediately)
•Ann Arbor Stage I-IV
•In case of prior treatment with Rituximab, the presence of CD20 on lymphoma cells
must have been demonstrated before inclusion in the trial.
•ECOG performance status of 0,1 or 2
•Age > 18 years
•Life expectancy of at least 3 months
•Patient must be able to take aspirin daily as prophylactic anticoagulation (patients intolerant to ASA (may use warfarin or low molecular weight heparin)
•Hematological test results within these ranges:
Absolute neutrophil count equal/higher than 1000/µl
Platelet count egaul/higher 60 x 109/L
•Adequate cardiac, renal and liver function tests (LVEF > 50%, serum creatinine < 2.5
mg/dl, ALAT or ASAT < 2.5 x upper limit of normal range, alkaline phosphatase < 2.5 x upper limit of normal range, serum bilirubin < 2.0 mg/dl)
•Patient must be willing and able to comply with the protocol for the entire study duration
•Female subjects of childbearing potential† must:
understand the potential teratogenic risk to the unborn child
agree to have a medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL (including females of childbearing potential who commit to complete abstinence) details see appendix 6
agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation.
The two methods of reliable contraception must include one highly effective method and one additional effective (barrier) method. FCBP must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:
•Highly effective methods:
Intrauterine device (IUD)
Hormonal (birth control pills, injections, implants)
Tubal ligation
Partner’s vasectomy
•Additional effective methods:
Male condom
Diaphragm
Cervical Cap
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia.
be informed and understand the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy
understand the need to commence the study treatment as soon as study drug is dispensed following a negative pregnancy test
understand the need and accepts to undergo pregnancy testing based on the frequency outlined in this protocol
acknowledge that she understands the hazards and necessary precautions associated with the use of lenalidomide
•Male subjects must
Understand the need for the use of a condom even if he has had a vasectomy, if engaged in sexual activity with a pregnant female or a female of childbearing potential.
Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
•All subjects must
Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
Agree not to share study medication with another person and to return all unused study drug to the investigator
|
|
| E.4 | Principal exclusion criteria |
No patient may be included into the study if she/he fulfills any of the following criteria:
•Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse
large cell lymphoma (“high grade lymphoma”) - component
•Use of any investigational agent within 28 days prior to initiation of treatment with lenalidomide
•History of malignancy other than squamous cell carcinoma, basal cell carcinoma of
the skin or carcinoma in situ of the cervix within the last 5 years
•Major surgery, other than diagnostic surgery, within the last 4 weeks
•Evidence of CNS involvement
•A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
•Severe peripheral polyneuropathy
•Clinically significant cardiac disease (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
•Inadequate hematological status at baseline prior to study entry: Dependency on red
blood cell and/or platelet transfusions, ANC (absolute neutrophil count (segmented + bands)) <1.0 x 109/L
•Patients with active opportunistic infections
•Pregnancy
•Uncontrolled diabetes mellitus
•Preexisting thromboembolic events at start of study
•Known hypersensitivity to thalidomide or lenalidomide or rituximab
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Determination of percentage objective responders in patients with MALT lymphoma treated with the combination therapy of Rituximab and lenalidomide |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 | 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 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 | 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
|
| Study end will be at last patient last visit at final staging about 4 weeks after end of last cycle. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 1 |
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