Sonntag, 5. Mai 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE
AlloRelapseMM

Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy

Rekrutierend

NCT-Nummer:
NCT05675319

Studienbeginn:
März 2023

Letztes Update:
26.04.2024

Wirkstoff:
Allogeneic Stem Cells, carfilzomib/lenalidomide/dexamethasone (KRD), elotuzumab/lenalidomide/dexamethasone (ERD), daratumumab/bortezomib/dexamethasone (DVD), daratumumab/lenalidomide/dexamethasone (DRD), ixazomib/lenalidomide/dexamethasone (IRD), pomalidomide/bortezomib/dexamethasone (PVD), carfilzomib/daratumumab/dexamethasone (KDD), Autologous Stem Cells, daratumumab/pomalidomide/dexamethasone (DPD), isatuximab/carfilzomib/dexamethasone (Isa-KD), selinexor/bortezomib/dexamethasone (SVD)

Indikation (Clinical Trials):
Multiple Myeloma, Neoplasms, Plasma Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Universitätsklinikum Hamburg-Eppendorf

Collaborator:
Gemeinsamer Bundesausschuss (G-BA), Staburo GmbH,

Studienleiter

Nicolaus Kröger, Prof. Dr.
Principal Investigator
University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

Kontakt

Studienlocations
(3 von 31)

Munich Hospital Schwabing
80804 München
(Bayern)
GermanyZurückgezogen» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The primary objective of the present clinical study aims to demonstrate the superiority of

allogeneic stem cell transplantation (allo SCT) compared to conventional therapy for the

difference in overall survival (OS) at 5 years in patients with multiple myeloma who have

relapsed or progressed after first-line autologous hematopoietic stem cell therapy.

The secondary objectives are to show an improvement of progression free survival and relapse

free survival after allo SCT compared to conventional therapy.

In addition, quality of life, toxicities, recurrence rates, non-relapse mortality (NRM),

remission rates including minimal residual disease (MRD) and incidence of severe or

life-threatening infection between the two arms are compared. Acute and chronic

graft-versus-host disease (GvHD) after allo SCT are evaluated.

Ein-/Ausschlusskriterien

Inclusion Criteria:

Patients eligible for study inclusion must meet criteria 1- 7 at registration and all of

the following criteria before randomization:

1. Multiple Myeloma

2. Age 18 - 65 years

3. A signed informed consent form must be obtained before participation in the study

4. Age 66 - 70 years, if comorbidity index according to Sorror score = 0 and ECOG ≤ 1

5. 1st relapse/ progression according to IMWG criteria after first-line therapy

(consisting of induction therapy followed by autologous transplantation once or twice

and maintenance therapy), Additionally: meeting the need for treatment based on the

SLiM-CRAB-criteria

6. Negative pregnancy test in female patients

7. Maximum of 1 cycle salvage therapy prior to study inclusion

8. Availability of a fully compatible stem cell donor (HLA-ident. Sibling or 10/10 MUD or

9/10 MMUD if mismatch affects DQB) after 3 cycles salvage therapy

9. CR/PR or SD according to IMWG-criteria after 3 cycles salvage therapy within the study

Exclusion Criteria:

Patients are excluded from the study if any one of criteria 1-6 are met at registration and

if criterion 7 is met before randomization:

1. Non-sufficient organ function defined as:

Bilirubin (in the absence of Meulengracht's disease), SGPT or SGOT ≥3 higher than

normal values Cardiac ejection fraction ≤ 50% GFR < 30 ml/min DLCO < 35 % or

continuous oxygen dependency

2. Active hepatitis B or C infection or uncontrolled HIV infection

3. Other, active malignant disease

4. Prior treatment with allogeneic stem cells

5. Participation in a clinical trial or taking an IMP within 30 days or five times the

half-life of the IMP, whichever is longer, prior to registration

6. Positive serum pregnancy test at screening and before first treatment or breastfeeding

7. PD under salvage therapy

Studien-Rationale

Primary outcome:

1. Overall survival at five years after randomization (Time Frame - at 5 years after randomization):
The present clinical study aims to demonstrate the superiority of allogeneic stem cell transplantation compared to conventional therapy for the difference in overall survival at 5 years in patients with multiple myeloma who have relapsed or progressed after first-line autologous hematopoietic stem cell therapy.



Secondary outcome:

1. Event-free survival at 1 year after randomization (Time Frame - from randomization to 1 year after randomization):
A secondary objective is to show an improvement of progress free survival and relapse free survival after allogeneic stem cell transplantation compared to conventional therapy. Events are defined as: Progression or Relapse or Engraftment Failure or Death of any cause

2. Event-free survival at 3 years after randomization (Time Frame - from randomization to 3 years after randomization):
A further secondary objective is to show an improvement of progress free survival and relapse free survival after allogeneic stem cell transplantation compared to conventional therapy. Events are defined as: Progression or Relapse or Engraftment Failure or Death of any cause

3. Event-free survival at 5 years after randomization (Time Frame - from randomization to 5 years after randomization):
A secondary objective is to show an improvement of progress free survival and relapse free survival after allogeneic stem cell transplantation compared to conventional therapy. Events are defined as: Progression or Relapse or Engraftment Failure or Death of any cause

4. Change from baseline in total EORTC score at 1 year after randomization (Time Frame - at visit Screening, at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months and 12 months after randomization):
The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups.. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for final analysis and adjusted mean calculated at 1 year after randomization.

5. Change from baseline in total EORTC score at 3 years after randomization (Time Frame - at visit Screening, at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months, 1 year, 2 years and 3 years after randomization):
The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for final analysis and adjusted mean calculated at 3 years after randomization.

6. Change from baseline in total EORTC score at 5 years after randomization (Time Frame - at visit Screening, at the end of cycle 3 (84 days, each cycle is 28 days) of salvage therapy, 6 months, 1, 2, 3, 4 and 5 years after randomization):
The aim of the quality of life questionnaires (QLQ) is to provide a comparison between the two treatment arms. Quality of life according EORTC (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) & Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20)) will be assessed in both groups. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology/ sickness. Patients will be observed from baseline until database lock for final analysis and adjusted mean calculated at 5 years after randomization.

7. Time to first occurrence of remission after randomization (Time Frame - at 30 days, 100 days, 6 months, 1 and 2 years after randomization):
Patients will be followed from randomization until database lock for final analysis and cumulative incidence of first remission (partial or complete), at 2 years after randomization, is reported.

8. Non-relapse mortality (NRM) at 1 year after randomization (Time Frame - from randomization to 1 year after randomization, an average of 1 year):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of death before any relapse at 1 year after randomization was reported.

9. Non-relapse mortality (NRM) at 3 years after randomization (Time Frame - from randomization to 3 years after randomization, an average of 3 years):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of death before any relapse at 3 years after randomization was reported.

10. Non-relapse mortality (NRM) at 5 years after randomization (Time Frame - from randomization to 5 years after randomization, an average of 5 years):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of death before any relapse at 5 years after randomization was reported.

11. Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 1 year after randomization (Time Frame - at 30 days, 100 days, 6 months and 1 year after randomization, an average of 1 year):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any acute Graft-versus-Host Disease (GvHD, according to Przepiorka et al.) at 1 year after randomization is reported

12. Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 3 years after randomization (Time Frame - at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months and 3 years after randomization, an average of 3 years):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any acute GvHD (according to Przepiorka et al.) at 3 years after randomization is reported

13. Cumulative incidence of acute GvHD after allogeneic stem cell transplantation at 5 years after randomization (Time Frame - at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months, 3, 4 and 5 years after randomization, an average of 5 years):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any acute GvHD (according to Przepiorka et al.) at 5 years after randomization is repoted.

14. Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 1 year after randomization (Time Frame - at 30 days, 100 days, 6 months and 1 year after randomization, an average of 1 year):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 1 year after randomization is reported.

15. Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 3 years after randomization (Time Frame - at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months and 3 years after randomization, an average of 3 years):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 3 years after randomization is reported.

16. Cumulative incidence of chronic GvHD after allogeneic stem cell transplantation at 5 years after randomization (Time Frame - at 30 days, 100 days, 6 months, 1 year, 18 months and 2 years, 30 months, 3, 4 and 5 years after randomization, an average of 5 years):
Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any chronic GvHD (according to Jagasia et al.) at 5 years after randomization is reported.

17. Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 1 year after randomization (Time Frame - from randomization to 1 year after randomization, an average of 1 year):
The severity and/or intensity of an adverse event will be graded based upon the patient's symptoms according to the current active version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any infectious complication with CTCAE grade 3 - 5 at 1 year after randomization is reported.

18. Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 3 years after randomization (Time Frame - from randomization to 3 years after randomization, an average of 3 years):
The severity and/or intensity of an adverse event will be graded based upon the patient's symptoms according to the current active version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any infectious complication with CTCAE grade 3 - 5 at 3 years after randomization is reported.

19. Time to first occurrence of infection reported as cumulative incidence of infection with CTCAE grade 3 - 5 at 5 years after randomization (Time Frame - from randomization to 5 years after randomization, an average of 5 years):
The severity and/or intensity of an adverse event will be graded based upon the patient's symptoms according to the current active version of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Patients will be observed from randomization until database lock for final analysis and cumulative incidence of any infectious complication with CTCAE grade 3 - 5 at 5 years after randomization is reported.

Studien-Arme

  • Experimental: Arm A (allo SCT)
    Allogeneic stem cell transplantation
  • Active Comparator: Arm B (conventional therapy)
    Currently approved triple regimens for first relapse: carfilzomib/lenalidomide/dexamethasone (KRD) or elotuzumab/lenalidomide/dexamethasone (ERD) or daratumumab/bortezomib/dexamethasone DVD) or daratumumab/lenalidomide/dexamethasone (DRD) or ixazomib/lenalidomide/dexamethasone (IRD) or pomalidomide/bortezomib/dexamethasone (PVD) or carfilzomib/daratumumab/dexamethasone (KDD) or daratumumab/pomalidomide/dexamethasone (DPD) or isatuximab/carfilzomib/dexamethasone (Isa-KD) or selinexor/bortezomib/dexamethasone (SVD) Alternatively, autologous stem cell transplantation may also be performed, if sufficient stem cells are still cryopreserved.

Geprüfte Regime

  • Allogeneic Stem Cells:
    Allogeneic Stem Cell Transplantation
  • carfilzomib/lenalidomide/dexamethasone (KRD):
    triple regimen for first relapse should be applied according to latest Summary of Product Characteristics (SmPC) version
  • elotuzumab/lenalidomide/dexamethasone (ERD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • daratumumab/bortezomib/dexamethasone (DVD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • daratumumab/lenalidomide/dexamethasone (DRD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • ixazomib/lenalidomide/dexamethasone (IRD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • pomalidomide/bortezomib/dexamethasone (PVD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • carfilzomib/daratumumab/dexamethasone (KDD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • Autologous Stem Cells:
    Autologous Stem Cell Transplantation
  • daratumumab/pomalidomide/dexamethasone (DPD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • isatuximab/carfilzomib/dexamethasone (Isa-KD):
    triple regimen for first relapse should be applied according to latest SmPC version
  • selinexor/bortezomib/dexamethasone (SVD):
    triple regimen for first relapse should be applied according to latest SmPC version

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.