| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| relapsed multiple myeloma |
|
| 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 | 18.0 |
| 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 determine maximum tolerated dose (MTD) of CY (PO and IV) in combination with LEN and low-dose DEX
• To investigate best objective response (EBMT criteria) of both treatment regimens
|
|
| E.2.2 | Secondary objectives of the trial |
• To investigate safety and tolerability 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 ≥ 18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Previously diagnosed with multiple myeloma based on standard criteria and requires therapy for primary refractory disease or 1st – 3rd relapse because of progressive disease (PD), defined as a 25% increase in M-protein, development of new or worsening of existing lytic bone lesions or soft tissue plasmacytoma, or hypercalcemia (serum calcium > 11.3 mg/dL), or clinical relapse from CR.
5. At least one measurable disease manifestation defined as follows:
• For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value (generally, but not exclusively, > 1g/dL IgG M-protein or > 0.5 g/dL IgA) and, where applicable, urine light-chain excretion of ≥ 200 mg/24 h.
• For oligo- or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or a quantifiable plasma cell infiltration of the bone marrow as determined by bone marrow biopsy.
6. ECOG performance status of <= 2 at time of randomization/registration
7. Laboratory test results within these ranges within 1 week prior to randomization/registration:
• Absolute neutrophil count ≥ 1.5 x 109/L without the use of colony stimulating factors within 14 days before the laboratory test.
• Platelet count ≥ 75 x 109/L without transfusion support within 14 days before the laboratory test.
• Hemoglobin ≥ 7.5 g/dL (regardless of transfusion support or prior medication with erythropoietin).
• Calculated creatinine clearance ≥ 50 mL/minute.
• Total bilirubin <= 1.5 mg/dL.
• AST (SGOT) and ALT (SGPT) <= 2,5 x ULN.
• Corrected serum calcium < 14 mg/dL (< 3.5 mmol/L).
8. Contraception for females of childbearing potential and male subjects (For details see protocol)
9. Disease free of prior malignancies for ≥ 5 years with exception of treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast
10. Able and willing to take heparin (usually low-molecular weight - LMWH) or low acetylsalicylic acid (100 mg) daily as prophylactic anticoagulation.
11. 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 breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
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/registration 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 cyclophosphamide.
6. Any prior use of lenalidomide.
7. Concurrent use of other anti-cancer agents or treatments.
8. Known positive for HIV or currently active hepatitis, type A, B or C.
9. Any other chemotherapy or high-dose dexamethasone within 4 weeks before randomization/registration.
10. Immunotherapy or antibody therapy within 8 weeks before randomization/registration.
11. Major surgery within 4 weeks before randomization/registration.
12. Myocardial infarction within 6 months before randomization/registration, New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
13. Cardiac amyloidosis.
14. 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.
15. Any systemic infection requiring treatment.
16. Cystitis.
17. Disturbance of urinary flow.
18. Unable or unwilling to take heparin (usually low-molecular weight - LMWH) or low acetylsalicylic acid (100 mg) daily as prophylactic anticoagulation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Maximum tolerated dose (MTD) (Procedures to determine MTD see protocol)
• Best objective response according to EBMT criteria
|
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| 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) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| 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 | 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
|
| Provided in the protocol (chapter 5.7 / 5.8) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| 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 | 6 |
| 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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