E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myeloablative haplo-identical stem cell transplantation for poor risk non-hodgkin lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Myeloablative haplo-identical stem cell transplantation for poor risk non-hodgkin lymphoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 assess the probability of PFS defined as the proportion of being alive and free of relapse at 1 year after haplo-HSCT with ptCY |
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E.2.2 | Secondary objectives of the trial |
- To assess the Kaplan-Meier-Estimate probability of PFS over time up to the maximum Follow-up period - To assess the combined probability of relapse and non-relapse mortality over time by defining relapse and non-relapse mortality as competing risks to each other -To assess the probability of OS defined as the proportion being alive at 1 year after registration with ptCY - To assess the Kaplan-Meier-Estimate of OS over time up to the maximum Follow-up period - To assess the probability over time and severity of acute and chronic GvHD over time -To assess the safety of ptCY |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent obtained according to international guidelines and local laws; 2. Male or female patients aged 18-65 years; 3. Diagnosis of one the following NHL subtypes (PTCL, DLBCL, MCL, FL, transformed CLL) 4. Refractoriness or early relapse (<12 months) after at least two regimens and/or auto-HSCT failure; 5. Intent-to Thiotepa based myeloablative Haplo-HSCT because of unavailability of a fully matched SIB or MUD (10/10), within the time frame for successful HSCT as determined by disease activity; 6. Eligible to undergo myeloablative allogeneic stem cell transplantation as judged by the treating transplant physician. E.g. patients with controlled clinically insignificant infections are eligible, whereas patients with active uncontrolled infections are not eligible. 7. ECOG performance status of 0 - 1; 8. Ability to understand the nature of the trial and the trial related procedures and to comply with them. |
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E.4 | Principal exclusion criteria |
1. Patients with known congestive heart failure NYHA Class III and IV 2. Known HIV infection, infectious hepatitis (type B or C) or any other uncontrolled severe infection, i.e. patients with positive HIV test or active hepatitis B should be excluded. Only patients positive for anti-HBs+ with or without anti-HBc+ are allowed to enter the study. Patients with hepatitis C (anti-HCV+) should be excluded; 3. Known hypersensitivity to cyclophosphamide; 4. Renally impaired patients with creatinine clearance < 30 ml/min (Cockcroft-Gault equation); 5. Simultaneous participation in other clinical trials; 6. Participation in a clinical trial within the last 14 days before the date of registration of this trial; 7. Known abuse of medication, drugs or alcohol; 8. Female patients who are pregnant or breast feeding; 9. Fertile patients refusing to use safe contraceptive methods during the study. 10. Patients with uninary outflow obstructions or clinical signs of cystitis are not eligible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival defined as being alive and free of relapse at 1 year post haplo-stem cell transplantation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year post haplo-stem cell transplantation |
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E.5.2 | Secondary end point(s) |
1. Progression free survival defined as the period between registration and progression or death, whichever occurs first 2. Time to relapse defined as the period between registration and relapse 3. Time to non-relapse mortality (NRM) defined as the period between registration and non tumor-related death 4. Overall survival defined as being alive at 1 year after registration 5. Overall survival defined as the period between registration and death by any cause 6. Time to and severity of acute and chronic GvHD post haplo-HSCT 7. Type, frequency, severity and relationship of adverse events to study treatment, engraftment, infections
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3, 5-7: Day 30, Day 100, Month 6, month 9, month 12 post haplo-stem cell transplantation 4: 1 year post haplo-stem cell transplantation |
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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 | 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 | 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) | No |
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 | 10 |
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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |