| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| primary treatment of multiple myeloma patients of age 60 till 75 years |
|
| E.1.1.1 | Medical condition in easily understood language |
| Erstbehandlung des Multiplen Myeloms bei Patienten im Alter von 60 bis 75 Jahren |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 compare the efficacy of both treatment regimens with regard to progression-free
survival. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the safety and overall survival of both treatment regimens.
• To investigate other efficacy parameters of both treatment regimens. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Understand and voluntarily sign an informed consent form
2. Age 60-75 years.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Symptomatic multiple myeloma requiring therapy
5. Measurable monoclonal protein present in serum and/or urine
6. Monoclonal plasma cells in the bone marrow ≥ 10% and/or biopsy-proven plasmacytoma
7. Myeloma-related organ dysfunction, at least one of
[C] Calcium elevation in the serum (> 11.5 mg/dL or > 2.65 mmol/l)
[R] Renal insufficiency (creatinine > 2mg/dL or > 173 µmol/l)
[A] Anemia (Hb < 10 g/dL or 2 g/dL < normal)
[B] Bone lesions or general osteoporosis
8. ECOG performance status of ≤ 2 at time of randomization
9. Laboratory test results within these ranges within 1 week prior to
randomization/registration:
• Absolute neutrophil count ≥ 1.0x10e9/L
• Platelet count ≥ 75 x 10e9/L or in case of bone marrow infiltration with myeloma cells ≥ 30x10e9/L
• Total bilirubin ≤ 2mg/dL
• AST and ALT ≤ 3xULN
10. Female subjects of childbearing potential must:
o Understand the study drug has a teratogenic risk to the unborn child
o 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
lenalidomide; 2) while taking lenalidomide; 3) during dose
interruptions; and 4) for at least 28 days after last dose of
lenalidomide . The two methods of reliable contraception must
include one highly effective method and one additional effective
(barrier) method. The following are examples of highly effective and additional effective methods of contraception:
Examples of highly effective methods:
- Intrauterine device (IUD)
- Hormonal (birth control pills, injections, implants, levonorgestrel-releasing intrauterine System [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g.
desogestrel]))
- Tubal ligation
- Partner’s vasectomy
Examples of additional effective methods:
- Male condom
- Diaphragm
- Cervical Cap
o Agree to have two medically supervised negative pregnancy tests
(sensitivity of at least 25 mIU/mL) prior to starting lenalidomide. The
first pregnancy test must be performed within 10 to 14 days prior to
the start of lenalidomide and the second pregnancy test must be
performed within 24 hours prior to the start of lenalidomide. The
patient may not receive lenalidomide until the study doctor has
verified that the results of these pregnancy tests are negative. This
requirement also applies to women of childbearing potential who
practice complete and continued abstinence. The test should ensure the subject is not pregnant when she starts treatment.
o Agree to have a medically supervised pregnancy test weekly for the
first 28 days of study participation and then every 28 days while taking
lenalidomide, at study discontinuation, and at day 28 following the last dose of lenalidomide. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days of study participation and then every 14 days while taking lenalidomide, at study discontinuation, and at days 14 and 28 following the last dose of
lenalidomide.
o Should not donate blood while receiving lenalidomide, during dose
interruptionsand for at least 28 days after the last dose of lenalidomide.
o Counseling about pregnancy precautions and the potential risks of
fetal exposure must be conducted at a minimum of every 28 days.
o If pregnancy or a positive pregnancy test does occur in a study patient, lenalidomide must be immediately discontinued.
o Pregnancy testing and counseling must be performed if a patient
misses her period or if her pregnancy test or her menstrual bleeding is
abnormal. Lenalidomide must be discontinued during this evaluation.
o Females must agree to abstain from breastfeeding while taking
lenalidomide and for at least 28 days after the last dose of
lenalidomide.
Male subjects
o Must understand the potential teratogenic risk if engaged in sexual
activity with a pregnant female or a FCBP.
o Must practice complete abstinence or use a condom during sexual contact with a pregnant female or a female of childbearing potential while taking lenalidomide, during dose interruptions and for at least 28 days after the last dose of lenalidomide, even if he has undergone a successful vasectomy.
o Must not donate blood, semen or sperm while receiving lenalidomide, during dose interruptions or for at least 28 days after the last dose of lenalidomide.
11. Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast.
12. Able to receive antithrombotic prophylaxis.
13. Life-expectancy > 3 months. |
|
| E.4 | Principal exclusion criteria |
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.
2. Pregnant or lactating females
3. Any condition, including the presence of laboratory abnormalities, which places
the subject at unacceptable risk if he/she were to participate in the study or
confounds the ability to interpret data from the study
4. Patient currently is enrolled in another clinical research study or has been enrolled
in such a study within 4 weeks before randomization and/or is receiving an investigational agent for any reason or has received such an agent
within 4 weeks before randomization/registration
5. Known hypersensitivity to thalidomide, dexamethasone, or melphalan
6. The development of erythema nodosum if characterized by a desquamating rash
while taking thalidomide or similar drugs
7. Any prior use of lenalidomide
8. Concurrent use of other anti-cancer agents or treatments, with the exception of radiotherapy to restricted areas
9. Known positive for HIV; active or chronic hepatitis A, B or C infection (including patients who are tested anti-HBc positive and/or HBsAg positive) - serological testing for hepatitis A, B, C required
10. Prior treatment with dexamethasone discontinued because of ≥ grade 3
dexamethasone-related toxicity
11. Any prior chemotherapy with the exception of a short course of dexamethasone for symptom control
12. Immunotherapy or antibody therapy within 8 weeks before
randomization
13. Major surgery within 4 weeks before randomization
14. Renal failure requiring dialysis
15. Myocardial infarction within 6 months before randomization/registration, NYHA Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities
16. Severe pulmonary disease (diffusion capacity < 50% of normal)
17. Treatment for cancer other than multiple myeloma within 5 years before
randomization, with the exception of basal cell carcinoma or cervical
cancer in situ
18. Cardiac amyloidosis
19. Poorly controlled hypertension, diabetes mellitus, or other serious medical or
psychiatric illness that could potentially interfere with the completion of treatment
according to the protocol
20. Any systemic infection requiring treatment
21. Unability or unwillingness of the patient to receive antithrombotic prophylaxis |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| progression-free survival (PFS) from the time point of randomization |
|
| E.5.2 | Secondary end point(s) |
- Overall survival (OS)
- Response (complete response [CR], stringent complete response [sCR] very good
partial response [VGPR], partial response [PR], and overall response [CR
(including sCR) + VGPR + PR]) according to IMWG criteria (27).
- Duration of response
- Time to response
- Safety (adverse events, laboratory abnormalities, and hospitalizations)
- Time to treatment failure (TTF)
- Time to progression (TTP)
- Time to second-line anti-myeloma treatment
- Relationship of cytogenetic findings in the malignant myeloma clone at baseline
to clinical outcomes |
|
| 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 | 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) | 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 |
| comparisan of lenalidomide and dexamethason with or w/o intensification by high-dose melphalan |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 40 |
| 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 | 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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