E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
multiple myeloma |
mieloma multiplo |
|
E.1.1.1 | Medical condition in easily understood language |
multiple myeloma |
mieloma multiplo |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
Percentage of patients collecting ≥ 6 x 106 CD34+ cells/Kg in three or less apheresis |
Percentuale di pazienti in grado di raccogliere ≥ 6 x 106 cellule CD34+ /Kg in tre o meno di tre procedure aferetiche |
|
E.2.2 | Secondary objectives of the trial |
Number of apheresis to collect ≥ 6 x 106 CD34+ cells/Kg
Evaluation of engraftment after transplantation of plerixafor-mobilized PBSCs
Evaluation of immunological reconstitution after transplantation
Evaluation of cellular graft content
Evaluation of resources consumption and relative direct costs estimation in the management of patients with plerixafor therapy in association with G-CSF after chemotherapy
Percentage of patients collecting ≥ 4 x 106 CD34+ cells/Kg in three or less apheresis following rescue strategy (plerixafor + G-CSF), and number of apheresis required |
Numero di aferesi necessarie per raccogliere ≥ 6 x 106 cellule CD34+/Kg
Valutazione dell’attecchimento dopo trapianto di PBSCs mobilizzate con plerixafor
Valutazione della ricostituzione immunologica dopo trapianto
Valutazione del tipo di cellule presenti nelle leucoaferesi di cellule staminali
Valutazione del consumo di risorse sanitarie e stima dei relativi costi diretti nella gestione dei pazienti in terapia con Plerixafor e G-CSF dopo chemioterapia
Percentuale di pazienti in grado di raccogliere ≥ 4 x 106 cellule CD34+/Kg in tre o meno di tre procedure aferetiche dopo strategia di mobilizzazione di salvataggio con plerixafor + G-CSF, e numero di aferesi necessarie |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• MM patients eligible and planned for ASCT according to Istitutional guidelines
• Age > 18 years
• Written informed consent
• Performance Status ≥ 70% (Karnofsky) or ≤ 2 (WHO).
• White blood cell (WBC) count ≥ 2.5 x 109 /L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
• Platelet count ≥ 100 x 109 /L
• Serum creatinine at time of enrollment ≤ 2.0 mg/dL
• Aspartate aminotransferase/serum glutamnic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamnic pyruvic transaminase (ALT/SGPT), and total bilirubin at time of enrollment < 2.5 x upper limit of normal (ULN)
• Adequate cardiac, renal and pulmonary function to undergo apheresis and transplantation
• All patients must agree to use highly effective method of contraception while on study treatment and for at least 3 months following plerixafor treatment (including both female patients of child-bearing potential and male patients with partners of child-bearing potential). |
• Pazienti affetti da MM eleggibili e candidati a trapianto autologo secondo le linee guida di ogni Centro partecipante allo studio
• Età > 18 anni
• Consenso informato scritto
• Performance Status ≥ 70% (Karnofsky) o ≤ 2 (WHO).
• Numero di globuli bianchi (GB) ≥ 2.5 x 109 /L
• Numero assoluto di granulociti neutrofili (PMN) ≥ 1.5 x 109 /L
• Numero di piastrine ≥ 100 x 109 /L
• Creatinina sierica al momento dell’ arruolamento ≤ 2.0 mg/dL
• Aspartato aminotransferasi/glutamnico ossalacetico transaminasi sierica (AST/SGOT), alanina aminotransferasi/glutamnico piruvico transaminasi sierica (ALT/SGPT), e bilirubina totale al momento dell’ arruolamento < 2.5 volte il limite superiore di normalità (ULN)
• Funzione cardiaca, renale, polmonare adeguata per essere sottoposto a procedura aferetica e trapianto.
• Tutti i pazienti devono accettare di utilizzare metodi di contraccezione altamente efficaci durante il trattamento dello studio e per almeno 3 mesi dopo trattamento con plerixafor (sono incluse le pazienti in età fertile e i pazienti con partner fertili). |
|
E.4 | Principal exclusion criteria |
• History of any acute or chronic myelogenous leukemia
• HIV positivity; active Hepatitis B or Hepatitis C
• Intercurrent organ damage or medical problems that would interfere with therapy.
• Pregnant or nursing females.
• Concurrent uncontrolled infection.
• Previously received investigation therapy within 4 weeks of enrolling in this protocol or currently enrolled in another investigational protocol during the mobilization phase
• Treated with G-CSF or other cytokine within 14 days prior to the first dose of G-CSF for mobilization |
• Storia di una qualunque leucemia acuta o cronica.
• Positività nota al virus dell’immunodeficienza acquisita (HIV); epatite B o C attiva
• Condizioni di comorbidità o problemi clinici intercorrenti che potrebbero interferire con la terapia.
• Donne gravide o in allattamento.
• Infezione intercorrente non controllata.
• Somministrazione di una precedente terapia sperimentale entro 4 settimane dall’arruolamento nel presente protocollo o arruolamento in un altro protocollo sperimentale durante la fase di mobilizzazione.
• Trattamento con G-CSF o un’altra citochina nei 14 giorni precedenti la prima dose di G-CSF per la mobilizzazione. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of CD34+ cells mobilized into PB
Number of PBSC collections |
Numero di cellule CD34+ mobilizzate nel sangue periferico
Numero di procedure aferetiche |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Number of days to neutrophil and platelet engraftment.
Kinetic of immunological reconstitution as the number of circulating lymphocytes, CD3+ , CD4+, CD8+, CD19+ , T-reg and CD56+ cells at 30 days, 3,6,9 and 12 months after transplantation.
Concentration of stem cell and lymphocyte subsets into leukaphereses.
Type and quantity of medical resources and estimation of relative direct medical costs for plerixafor therapy in association with G-CSF after chemotherapy. |
Numero di giorni per l’attecchimento dei granulociti neutrofili e delle piastrine dopo ASCT.
Cinetica della ricostituzione immunologica, valutata come numero di linfociti circolanti, cellule CD3+ , CD4+, CD8+, CD19+ , T-reg e CD56+ a 30 giorni, 3,6,9 e 12 mesi dopo ASCT.
Concentrazione di cellule staminali e sottopopolazioni linfocitarie nell’aferesi
Tipologia e quantità di risorse e materiale sanitario consumato per la somministrazione di terapia con plerixafor in associazione a G-CSF dopo chemioterapia |
|
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 | Yes |
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 | 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
|
|
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 | 24 |
E.8.9.1 | In the Member State concerned days | 0 |