| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
Cancer affecting a sub-type of lymphocytes B (protect the body against
infections) that don't mature properly and multiply abnormally in the
lymph nodes (mantle zone) |
|
| 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 | 17.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10026798 |
| E.1.2 | Term | Mantle cell lymphomas |
| E.1.2 | System Organ Class | 100000004851 |
|
| 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 tumor response and duration of response of lenalidomide monotherapy in patients with mantle cell lymphoma (MCL) who have relapsed or progressed after treatment with bortezomib or are refractory to bortezomib (Cheson, 1999) |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate the safety of lenalidomide monotherapy in patients with
MCL who have relapsed or progressed after treatment with bortezomib
or are refractory to bortezomib
•To determine the CR, time to progression, time to treatment failure,
progression-free survival and overall survival of lenalidomide
monotherapy in patients with MCL who have relapsed or progressed
after treatment with bortezomib or are refractory to bortezomib |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Must understand and voluntarily sign an informed consent form.
2. Must be ≥ 18 years of age at the time of signing the informed consent form.
3. Must be able to adhere to the study visit schedule and other protocol requirements.
4. Biopsy-proven mantle cell NHL, including overexpression of cyclin D1 by immunohistochemistry or t(11;14)(q13;q32) by FISH. In patients whose tumors are negative for the cyclin D1 overexpression or translocation, overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable.
5. Must have received all of the following agents (alone or in combination). (There is no limit on the number of agents or prior therapies). The following agents can be given in any combination:
- Anthracycline or mitoxantrone
- Cyclophosphamide
- Rituximab
-Bortezomib
6. Patients must have documented relapsed, refractory or PD after treatment with bortezomib (or a bortezomib containing regimen) based on the following definitions:
- Relapsed lymphoma: patients with relapse within one year of last dose of bortezomib (or a bortezomib containing regimen) following initial response of CR to bortezomib (or a bortezomib containing regimen)
- Lymphoma refractory to bortezomib: patients with PD without any documented response of PR or better during treatment with bortezomib (or a bortezomib containing regimen) and having received at least 2 cycles of bortezomib (or a bortezomib containing regimen)
- Progressive disease: patients with PD within one year of last dose of bortezomib (or bortezomib containing regimen) following initial response of PR to bortezomib (or a bortezomib containing regimen)
7. Patients who have relapsed following high dose chemotherapy/autologous stem cell transplant are eligible.
8. Must have measurable disease on cross sectional imaging by CT that is at least 2 cm in the longest diameter and measurable in two perpendicular dimensions.
9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
10. Life expectancy of ≥ 90 days (3 months).
11. Females of child-bearing potential (FCBP) must agree to:
-Have two medically supervised pregnancy tests prior to starting of study therapy. The first pregnancy test will be performed within 10-14 days prior to the start of lenalidomide and the second pregnancy test will be performed within 24 hours prior to the start of lenalidomide. She must also agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the patient practices complete and continued sexual abstinence.
-Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
12. Male patients must:
-Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.
-Agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
13. All patients must:
-Have an understanding that the study drug could have a potential teratogenic risk.
- Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
-Agree not to share study medication with another person.
- Must be counseled about pregnancy precautions and risks of fetal exposure.
|
|
| E.4 | Principal exclusion criteria |
1. Diagnosis of lymphoma other than MCL.
2. Transformed lymphoma
3. Any of the following laboratory abnormalities.
- Absolute neutrophil count (ANC) < 1,500 cells/mm^3 (1.5 x 10^9/L).
- Platelet count < 60,000/mm^3 (60 x 10^9/L).
- Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) > 3.0 x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma
- Serum total bilirubin > 1.5 x ULN, except in cases of Gilbert’s Syndrome and documented liver involvement by lymphoma.
4. Calculated creatinine clearance (Cockcroft-Gault formula) of < 30 mL /min
5. Active central nervous system (CNS) lymphoma with the exception of those patients whose CNS lymphoma has been treated with chemotherapy, radiotherapy or surgery, have remained asymptomatic for 90 days (3 months) and demonstrate no CNS lymphoma as shown by lumbar puncture, CT are eligible. Patients with a history of CNS involvement or CNS symptoms will be required to have negative cerebrospinal fluid (CSF) cytology examination and a head CT during the screening period
6. Patients who are candidates for high dose chemotherapy/autologous or allogeneic stem cell transplant at the time of enrollment are not eligible.
Provided the determination is clearly documented in the patient’s source document, the patient is eligible if:
• the physician indicates that the patient is not appropriate for autologous or allogeneic transplant at the time of enrollment, or
• the patient has refused high dose chemotherapy/autologous or allogeneic transplant
7. Patients who have relapsed following allogeneic stem cell transplant and who have persistent donor hematopoiesis are not eligible
8. Patients should not be receiving corticosteroids except for prednisone ≤ 10 mg/day or equivalent for purposes other than treating MCL.
9. Patients not willing to take DVT prophylaxis.
10. Prior history of malignancies, other than MCL, unless the patient has been free of the disease for ≥ 5 years. Exceptions include the following:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
11. Known seropositive 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 vaccine are eligible.
12. Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring parenteral antibiotics
- Uncontrolled diabetes mellitus
- Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease)
- Unstable angina pectoris, angioplasty, stenting, or myocardial infarctions within 180 days (6 months)
- Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia. Patients with controlled atrial fibrillation that is asymptomatic are eligible.
13. Desquamating (blistering) rash while taking thalidomide
14. This exclusion criterion was removed with Amendment #1
15. Prior use of lenalidomide
16. Use of the following prior to initiation (day 1 cycle 1) of study drug:
- Prior chemotherapy within 2 weeks (with recovery of bone marrow function),
- Nitrosoureas within 6 weeks
- Antibody agents within 8 weeks
- Radioimmunoconjugate within 12 weeks
- Radiation therapy within 3 weeks (except for cranial RT and electron beam)
17. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
18. Pregnant or lactating females.
19. Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
20. Participation in another clinical trial during the pre-treatment and treatment phase of the study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Tumor response rate and duration of response (Radiological assessments as defined by the IWLRC 1999) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
• The primary analyses for response will be performed on the ITT and
MITT populations after all patients' complete 6 cycles or progress before completing 6 cycles.
• Duration of response will be analyzed at the time of the primary
analysis of response, but the primary analysis of duration of response
will be performed on the ITT and MITT populations after all patients enrolled in the study have completed at least one year or have dropped out before completing one year. |
|
| E.5.2 | Secondary end point(s) |
• Complete response (CR)/Complete Response unconfirmed (Cru) and
Duration of response
• Progression–free survival (PFS)
• Time to tumor progression (TTP)
• Time to treatment failure (TTF)
• Overall survival (OS)
• Safety |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be analyzed at the time of the primary analysis
of response. However, final analyses for PFS, TTP, TTF and OS will be
performed after 100% of the patients have died are lost to follow up or
have withdrawn consent or a maximum of 4 years from last patient
enrolled, which ever comes first.
Follow-up for second primary malignancies and OS will continue until
100% of the patients have died, are lost to follow up, have withdrawn consent, or a
maximum of 5 years from the last patient enrolled, whichever comes first. |
|
| 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 | Yes |
| 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 | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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.8.2.4 | 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 | No |
| 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 |
| Chile |
| Colombia |
| Israel |
| Singapore |
| Turkey |
| United States |
|
| 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
|
The study will be terminated at the end of the follow up phase: until
either 100% of the patients have died, are lost to follow up or have
withdrawn consent or a maximum of 5 years from last patient enrolled
(LPI), which ever comes first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| 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 | 8 |
| 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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