E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Myeloma Stage II or III according to Salmon and Durie |
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E.1.1.1 | Medical condition in easily understood language |
Multiple myeloma is a type of blood cancer that affects the plasma cells. In multiple myeloma, malignant plasma cells accumulate in the bone marrow. |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Event-free survival four years after auto-allo tandem-transplantation and maintenance therapy with thalidomide in comparison to those patients without a suitable donor, who will receive tandem autologous stem cell transplantation followed by thalidomide maintenance therapy. Any of the following occurrences will be considered an endpoint event: •recurrence or progression of the primary disease, •disease related mortality, or •treatment related mortality.
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E.2.2 | Secondary objectives of the trial |
•Incidence of acute graft-versus-host disease on day +100 after allogeneic stem cell trans¬plantation according to the acc. to the Glucksberg scale revised by Przepiorka et al. •Incidence of chronic graft-versus-host disease according to the revised Seattle criteria of Lee et al. at one and two years after allogeneic stem cell transplantation. •Toxicity of conditioning and of maintenance therapy according to adverse events according to the reporting guidelines as per NCI CTCAE •Cumulative incidence of relapse at four years after auto-allo and auto-auto stem cell transplantation. •Disease related mortality at four years after allogeneic stem cell transplantation. •Treatment related mortality at four years after allogeneic stem cell transplantation. •Overall survival at four years after allogeneic stem cell transplantation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Multiple Myeloma Stage II or III according to Salmon and Durie (see Protocol Appendix 30.5 on page 75) • Patient's age: 18 – 60 years. • Patient's written informed consent. • Compliance with “Thalidomide Pregnancy Prevention Plan for Subjects in Clinical Trials” (see Protocol Appendix 30.14 on page 118); becoming effective with protocol version August 27, 2015. • A maximum of eight chemotherapy cycles prior to registration (CR / PR / MR / or PD).(Melphalan containing regimen should be avoided as induction therapy)
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E.4 | Principal exclusion criteria |
•More than eight chemotherapy cycles prior to registration. •Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as •Total bilirubin, SGPT or SGOT > 3 times upper the normal level. •Left ventricular ejection fraction < 30 %. •Creatinine clearance < 30 ml/min. •DLCO < 35 % and/or receiving supplementary continuous oxygen. •Positive serology for HIV. •Pregnant or lactating women. •Participation in another trial at time of registration. •No HLA-identical or compatible related or unrelated donor (HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1) (one mismatch allowed). •Preceding autologous stem cell transplantation. •Age > 61 years.
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-free survival four years after auto-allo tandem-transplantation and maintenance therapy with thalidomide in comparison to those patients without a suitable donor, who will receive tandem autologous stem cell transplantation followed by thalidomide maintenance therapy. Any of the following occurrences will be considered an endpoint event: •recurrence or progression of the primary disease, •disease related mortality, or •treatment related mortality.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
four years after auto-allo tandem-transplantation |
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E.5.2 | Secondary end point(s) |
• Incidence of acute graft-versus-host disease on day +100 after allogeneic stem cell trans-plantation according to the acc. to the Glucksberg scale revised by Przepiorka et al.. • Incidence of chronic graft-versus-host disease according to the revised Seattle criteria of Lee et al. at one and two years after allogeneic stem cell transplantation. • Toxicity of conditioning and of maintenance therapy according to adverse events according to the reporting guidelines as per NCI CTCAE. • Cumulative incidence of relapse at four years after auto-allo and auto-auto stem cell transplantation. • Disease related mortality at four years after allogeneic stem cell transplantation. • Treatment related mortality at four years after allogeneic stem cell transplantation. • Overall survival at four years after allogeneic stem cell transplantation.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
four years after allogeneic stem cell transplantation except chronic graft-versus-host disease (one and two years after allogeneic stem cell transplantation) and acute graft-versus-host disease (on day +100 after allogeneic stem cell trans-plantation) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 |
No maintenance Therapy with Thalidomide |
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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 | 24 |
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 | 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
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Last Folow-up visit of the last patient (LVLS) |
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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 | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |