| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients With Newly Diagnosed Multiple Myeloma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
|
| 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 |
| 1. To evaluate toxicity and tolerability of lenalidomide after allografting 2. To evaluate efficacy of lenalidomide in inducing complete remission, defined as negative immunofixation, 12 months after allografting. |
|
| E.2.2 | Secondary objectives of the trial |
| 1. To evaluate overall-survival 2. To evaluate progression free survival 3. To evaluate event-free survival 4. To evaluate molecular remission rate, and to compare molecular remission rate in patients treated with lenalidomide after tandem auto-allo transplant and after double autologous transplant (study protocol RV-MM-PI-209): molecular remission is defined as the disappearance of the disease- and patient-specific molecular marker by polymerase chain reaction (PCR)-based assay, in both bone marrow and blood on two consecutive tests at least six weeks apart (see Appendix M for details). 5. To monitor minimal residual disease in patients achieving clinical CR with lenalidomide |
|
| 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 |
ALTRI SOTTOSTUDI: BIOLOGIA MOLECOLARE
|
|
| E.3 | Principal inclusion criteria |
| Patient Selection A. Inclusion criteria 1. Newly diagnosed multiple myeloma patients with an HLA identical sibling suitable for PBSC donation. 2. Complete cytogenetic analysis at diagnosis, including FISH analysis for chromosome deletions 13 and 17, and translocations (4;14) (11;14) and (14;16). 3. The patient must have the capacity to give informed consent. 4. Age >18 and < 65 5. If female, the patient is either postmenopausal since at least 24 consecutive months or surgically sterilized or she agrees to practice sexual abstinence or to use two reliable methods for contraception (e.g. a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) for the duration of study 6. If male, the patient agrees to practice sexual abstinence or to use a latex condom during any sexual contact with women of childbearing potential for the duration of study 7. Negative pregnancy test Donor Selection A. Inclusion criteria 1. HLA- identical sibling 2. Donor must consent to G-CSF administration and leukapheresis for PBSC allograft 3. Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) 4. Age <75, older donors may be considered after consultation with protocol principal investigator. 5. Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses 6. Ovulation inhibitory progesterone-only pills (i.e., desogestrel) * Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception. **prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection 3. Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days from the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. 4. Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence D. Male subjects must 5. Agree 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. 6. Agree not to donate semen during study drug therapy and for one week after end of study drug therapy. E. All subjects must 7. Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy. 8. Agree not to share study medication with another person and to return all unused study drug to the Investigator |
|
| E.4 | Principal exclusion criteria |
| Patient selection 1. Karnofsky score less than 60 (see appendix C), unless due solely to myeloma 2. Left ventricular ejection fraction less than 40%, or symptomatic coronary artery disease or other cardiac failure requiring therapy 3. Bilirubin greater than 2 X the upper limit of normal, or SGPT and SGOT > 4 X the upper limit of normal 4. DLCO < 40% (corrected) or receiving continuous supplemental oxygen. 5. Creatinine clearance < 40 cc/min at the time of initial autografting evaluation. 6. Patients with poorly controlled hypertension 7. Patients with active non-hematologic malignancies (except non-melanoma skin cancers). 8. Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a >20% risk of disease recurrence 9. Seropositive for HIV 10. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment Donor selection 1. Identical twin 2. Age less than 12 years 3. Pregnancy 4. Infection with HIV 5. Inability to achieve adequate venous access 6. Known allergy to G-CSF 7. Current serious systemic illness 8. Failure to meet common criteria for stem cell donation as described in the standard practice guidelines of EBMT. F. Pregnant or lactating females. Pregnancies Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or disease state) of a female subject or the female partner of a male subject occurring while the subject is on study drug, or within 30 days of the subject’s last dose of study drug, are considered immediately reportable events. Study drug is to be discontinued immediately and the subject instructed to return any unused portion of the study drug to the Investigator(s). The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Celgene S.r.l., ,. immediately by phone (Tel +39-02-91434340) and facsimile (Fax +39-02-63471119 or drugsafety-italy@celgene.com) using the Pregnancy Reporting Form. The female should be referred to a physician specialized or experienced in teratology for further evaluation and counseling. The Investigator(s) will follow the female subject until completion of the pregnancy, and must notify Celgene S.r.l, of the outcome of the pregnancy as a follow-up to the initial report. If the outcome of the pregnancy meets the criteria for immediate classification as a SAE (i.e., spontaneous or therapeutic abortion [any congenital anomaly detected in an aborted fetus is to be documented], stillbirth, neonatal death, or congenital anomaly [including that in an aborted fetus]), the Investigator(s) should follow the procedures for reporting SAEs (i.e., report the event to Celgene S.r.l, by telephone -Tel. +39-02-914343409 and facsimile -Fax +39-02-63471119 or drugsafety-italy@celgene.com- within 24 hours of the Investigator’s knowledge of the event). In the case of a live “normal” birth, Celgene S.r.l, should be advised by telephone and facsimile within 24 hours of the Investigator’s knowledge of the event. All neonatal deaths that occur within 30 days of birth should be reported, without regard to causality, as SAEs. In addition, any infant death after 30 days that the Investigator(s) suspects is related to the in utero exposure to the study drug should also be reported to Celgene S.r.l, by telephone (Tel. +39-02-91434340) and facsimile (Fax +39-02-63471119 or drugsafety-italy@celgene.com) within 24 hours of the Investigators’ knowledge of the event. If the female is found not to be pregnant, any determination regarding the subject’s continued participation in the study will be determined by the Investigator(s). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. To evaluate toxicity and tolerability of lenalidomide after allografting 2. To evaluate efficacy of lenalidomide in inducing complete remission, defined as negative immunofixation, 12 months after allografting. |
|
| 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 | No |
| 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) | 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.8.3 |
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 | 11 |
| 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
|
| NA NOTE Durata prevista della sperimentazione 6 mesi dall`interruzione di lenalidomide per l`ultimo paziente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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