E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
To evaluate engraftment of PBPC’s mobilized by two different fixed doses of pegfilgrastim and a by-weight dose of filgrastim |
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E.2.2 | Secondary objectives of the trial |
Assess the ability of two different fixed doses of pegfilgrastim to mobilize PBPC. Assess the safety of pegfilgrastim Assess VAD,Thal/Dex, Vel/Dex and VTD or any induction chemotherapy on autologous transplantation The following endpoints will be analysed overall and by induction chemotherapy type: Evaluate the CD34+ cells/kg yield in each leukapheresis Evaluate the number of leukaphereses to collect 2x106 CD34+ cells/kg and 4x106 CD34+ cells/kg Evaluate the proportion of subjects with platelet recovery ≥ 20x109/L in the absence of transfusion for at least 7 days Evaluate the proportion of subjects with ANC recovery of ≥ 0.5x109/L Evaluate the time to ANC 0.5x109/L for 3 consecutive days Evaluate the time to ANC 1.0x109/L Evaluate the time to platelet recovery (time to platelets ≥ 20x109/L in the absence of platelet transfusion support for at least 7 days) Evaluate the incidence and duration of hospitalization during mobilization phase and during post-transplant phase
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject achieving complete, partial or minimal response according to Bladé criteria (see Annex A) after 4 cycles of induction first line chemotherapy (VAD or Thal/Dex or Vel/Dex or VTD or any other induction chemotherapy) (response evaluation will be performed after finalization of 3rd or 4th VAd or between cycle 3 and 4 of Thal/Dex or between cycle 3 and 4 of Vel/Dex or between cycle 3 and 4 of VTD) • Aged 18-70 years • Subject has given voluntary written informed consent • Subject is in the investigator’s opinion, willing and able to comply with the protocol requirements • Subject has an ECOG < 3 • Subject has the following laboratory values at baseline: • Platelet count ≥ 50x109/L without transfusion support within 7 days before the laboratory test • Absolute neutrophil count (ANC) ≥1000 without the use of colony stimulating factors • Corrected serum calcium < 14 mg/dl • Aspartate transaminase (AST) ≤ 2.5xULN • Alanine transaminase (ALT) ≤ 2.5xULN • Total bilirubin ≤ 1.5xULN • Male or female subject who is post-menopausal, surgically sterilized or willing to use an acceptable method of birth control for the duration of the study
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E.4 | Principal exclusion criteria |
• Subject receiving colony stimulating factors • Subject underwent plasmapheresis within 4 weeks before enrolment • Subject had major surgery within 4 weeks before enrolment • Subject with amyloidosis • Subject with myocardial infarction within 6 months prior enrolment or with NHYA (New York Heart Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. • Subject treated for a cancer other than MM within 5 years before randomization (except basal cell carcinoma or in situ cervical uterine carcinoma) • Subject has another serious medical condition that could potentially interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery. • Compromised renal function as evidenced by measured or calculated creatinine clearance ≤ 50 ml/min • Sero-positive for HIV antibody • Subject known to be hepatitis B surface antigen positive or who has an active hepatitis C infection • Subject has an active systemic infection requiring treatment • Female subject is pregnant or breast feeding • Subject enrolled in another clinical trial and/or receiving an investigational agent that will contra-indicate the use of pegfilgrastim as either mobilization agent or hematological recovery agent. Subjects are allowed to simultaneously participate to non-investigational trials.
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of subjects with engraftment of PBPC mobilized by two different doses of pegfilgrastim (12 mg and 18 mg) given as a single administration compared to a standard daily by-weight dose of filgrastim (10µg/kg) after induction chemotherapy (VAD, Thal/Dex, Vel/Dex, VTD or any other induction chemotherapy) in subjects with multiple myeloma. Engraftment is defined as an ANC recovery of ≥ 0.5x109/L for 3 consecutive days and a platelet recovery of ≥ 20x109/L in the absence of platelet transfusion within 7 days. If a tandem transplant is planned, only the first transplantation will be assessed.
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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 | Information not present in EudraCT |
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 | 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 | 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) | 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.8.5 | The trial involves multiple Member States | Yes |
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
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End of the trial will be defined as the last patient visit (100 days after autologous transplantation). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |