E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053948 |
E.1.2 | Term | Hematopoietic stem cell mobilization |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024329 |
E.1.2 | Term | Leukemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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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 determine the feasibility of plerixafor 320 μg/kg subcutaneously and of plerixafor 320 μg/kg intravenously to harvest a sufficient number of CD34+ peripheral blood stem cells/kg recipient body weight. Feasibilty is defined as a minimum of 2.0x106/kg CD34+ cells in one or two phereses in at least 90% of the donors
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E.2.2 | Secondary objectives of the trial |
Donors: 1. To determine the efficacy (nr of CD34+ cells / liter processed blood volume)of plerixafor in both arms. 2. To determine the time interval that is required to obtain 2.0 x 106 CD34+ cells/kg . 3. To determine the number of CD34+ cells in the peripheral blood at regular intervals after the administration of plerixafor. 4. To determine the number of CD34+ cells in the peripheral blood and the apheresis product at regular intervals during the stem cell apheresis. 5. To determine the phenotype of plerixafor mobilized CD34+ cells both in peripheral blood and collected stem cells.
Patients: 1. To document engraftment 30, 60 and 90 days after transplantation with an allograft harvested after mobilization with plerixafor 320 μg/kg subcutaneously or intravenously. 2. To document hematopietic reconstitution. 3. To study chimerism in peripheral blood and T-cells 30, 60 and 90 days, and chimerism in bone marrow 90 days .
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Donors • HLA identical sibling donor • Age 18-60 years inclusive • Hematologic parameters within normal limits • Capable of undergoing leucapheresis: adequate venous access. Must be willing to undergo insertion of a central catheter should leucapheresis via peripheral vein be inadequate • Willing and able to have bone marrow aspiration if there is mobilization failure • Negative pregnancy test at study entry for women of childbearing potential • Willing and able to use adequate contraception during the mobilization and collection period • Written informed consent from donor
Patients • Age 18-65 years inclusive • Patients with a cytopathologically confirmed diagnosis of: - De novo Acute Myeloid Leukemia according to WHO classification in first complete remission (excluding acute promyelocytic leukemia) OR - Myelodysplasia refractory anemia with excess of blasts (RAEB) with IPSS ≥ 1.5 in first complete remission OR - Therapy related AML/RAEB in first complete remission OR - Biphenotypic leukemia in first complete remission OR - De novo B or T Lineage Acute Lymphatic Leukemia in first complete remission. • WHO performance score 0,1 or 2 • Patients should have an HLA- identical sibling donor • Life expectancy >3 months • Negative pregnancy test at study entry for women of childbearing potential • Willing and able to use adequate contraception • Written informed consent from patient |
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E.4 | Principal exclusion criteria |
Donors • Monozygotic twin • Unstable hypertension requiring more than 1 medication. • Positive serology for hepatitis C or HbsAg • Treatment with other investigational drugs • HIV positivity • Pregnant or breastfeeding female subject
Patients • Patients who are treated with a kinase-inhibitor • Cardiac dysfunction • Severe pulmonary dysfunction (CTCAE grade 3-4) • Severe neurological or psychiatric disease • Significant hepatic dysfunction • Significant renal dysfunction • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.) • Patient known to be HIV-positive • Pregnant or breast-feeding female patients. • Presence of other active malignancy or a history of active malignancy during the past 5 years, other than non melanoma skin cancer, stage 0 cervical carcinoma, or treated early-stage prostate cancer provided that prostate-specific antigen is within normal limits |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of donors in each arm with a successful harvest (≥2.0x106 CD34+ cells /kg). |
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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 | Yes |
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 | 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 |
plerixafor subcutaneously vs plerixafor intravenously |
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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 | 3 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |