| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chemosensitive diffuse large B-cell lymphomas (DLBCL), follicular lymphomas (FL), and mantle cell lymphomas (MCL) in first or second remission |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients can be included if their lymphoma disease (diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma) was already sensitive to chemotherapy at first time or a second time. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| 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 show a clinically meaningful reduction of lung toxicity - defined as a decrease of the diffusion capacity of the lung for carbon monoxide (DLCO) by 20% or more from baseline before ASCT - from 25% of patients in the BEAM group to 4% of patients in the BeEAM group at 3 months after ASCT. Use Dinakara equation for adjusting DLCO for hemoglobin |
|
| E.2.2 | Secondary objectives of the trial |
- To assess acute and late toxicity/adverse events (CTCAE 4.0) during entire study period
- To assess the hematologic engraftment after 3 months
- To assess early and late lung toxicity by pulmonary function tests, spiro- and ergometry, DLCO, HRCT and venous BGA after 3 and 12 months
- To perform cardiac assessment by ECHO (Echocardiography)/ECG (Electrocardiography)
- To assess the quality of life prior to ASCT (autologous stem cell transplantation) and 3 and 12 months thereafter.
- To assess overall survival and progression free survival after 12 months and then yearly. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Chemosensitive diffuse large B-cell lymphomas (DLBCL), follicular lymphomas (FL), and mantle cell lymphomas (MCL) in first or second remission
• Aged between 18 years and 75 years
• Neutrophils ≥ 1000/μl; Platelets ≥ 100 x 109/L |
|
| E.4 | Principal exclusion criteria |
• Acute uncontrolled infection
• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.) excluding a treatment according to this protocol
• HCTCI (hematopoietic cell transplantation comorbidity index) > 5 (Use Dinakara equation for adjusting DLCO for hemoglobin)
• Concurrent malignant disease with the exception of basalioma/spinalioma of the skin or early-stage cervix carcinoma or early-stage prostate cancer. Previous treatment for other malignancies (not listed above) must have been terminated at least 24 months before registration and no evidence of active disease must be documented since then.
• Known or suspected non-compliance excluding participation to the treatment as outlined in this protocol
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Major coagulopathy or bleeding disorder
• Major surgery less than 30 days before start of treatment
• Contraindications to the class of drugs under study, known hypersensitivity or allergy to class of drugs or the investigational product
• Women who are pregnant or breast feeding; Women with the intention to become pregnant during the course of the study,
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilized / hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| A clinically meaningful reduction of lung toxicity is defined as a reduction of the DLCO by at least 20% from baseline before ASCT. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At baseline before ASCT (Autologous stem cell transplantation), as well as 3 months and 12 months after ASCT |
|
| E.5.2 | Secondary end point(s) |
• Acute and late toxicity/adverse events are assessed according to the CTCAE 4.0 during the entire study period.
• Hematologic engraftment after ASCT is defined as the first day of neutrophils rising above 0.5 G/l, and of platelets rising above 20 G/L in the absence of platelet transfusions in the previous 3 days.
• Overall survival is defined as the time from ASCT until death of any cause or date of last follow-up.
• Progression free survival is defined as the time from ASCT until first recurrence of lymphoma or date of last follow-up whatever occurs first.
• Safety Outcomes
This study intends to assess cardiac and pulmonary toxicities associated with high-dose chemotherapy before autologous stem cell transplantation. Patients will be screened for the occurrence of such toxicities by pulmonary and cardiac assessments at specified time points during the study protocol.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Acute and late toxicity/adverse events (CTAE 4.0) during the entire study period
• Hematologic engraftment three months after ASCT
• Early and late lung toxicity at baseline before ASCT, as well as 3 months and 12 months after ASCT.
• Cardiac assessment at baseline before ASCT, as well as 3 months and 12 months after ASCT.
• Quality of life assessed at baseline before ASCT, as well as 3 months and 12 months after ASCT
• Overall survival and progression free survival after 12 months and then yearly as routine follow-up assessments.
• Safety outcomes up to 12 months after the last administration of study medication. |
|
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 2 |
| 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 | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
|
Last-Participant-Out (planned): December 2018
The final analysis of the study will be initiated 12 months after inclusion of the last study patient.
Overall survival and progression free survival data will be collected after 12 months and then yearly up to 10 years as routine follow-up assessments. Patients will be informed about this long term follow up within informed consent form. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 48 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 48 |
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