Auto-Allo Tandem Stem Cell Transplantation for Patients With Multiple Myeloma

Autologous-Allogeneic Tandem Stem Cell Transplantation and Maintenance Therapy With Thalidomide/ DLI for Patients With Multiple Myeloma (MM) and Age < _60 Years: A Phase II-study

The present study will be a multicenter, prospective phase II-study investigating safety and efficacy of the combination of auto-allo tandem stem cell transplantation in patients with multiple myeloma and age of >_60 years, followed by maintenance therapy with low-dose Thalidomide and Donor Lymphocyte Infusions.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Procedure: Auto-Allo Tandem SCT and maintenance therapy with Thalidomide/ DLI; Procedure: auto-auto Tandem stem cell transplantation and maintenance therapy with Thalidomide

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany, 86156
    • Klinikum Augsburg
  • Berlin, Germany, 12203
    • Charité
  • Dresden, Germany, 01307
    • Universitätsklinikum Dresden
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt (Oder), Germany, 15236
    • Klinikum Frankfurt (Oder) GmbH
  • Greifswald, Germany, 17475
    • Universitätsklinikum Greifswald
  • Göttingen, Germany, 37075
    • Universitätsklinikum Göttingen
  • Halle (Saale), Germany, 06097
    • Universitatsklinikum Halle (Saale)
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg-Eppendorf
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Marburg, Germany, 35032
    • Universitätsklinikum Marburg
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Stuttgart, Germany, 70376
    • Robert-Bosch-Krankenhaus
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik für Diagnostik
  • Wiesbaden, Germany, 65199
    • Horst Schmidt Kliniken GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Multiple Myeloma Stage II or III acc. to Salmon and Durie
• Patient's age 18-60 years
• Patient's written informed consent
• Women and men capable of reproduction must agree to use adequate contraceptive measures (condom, IUD, oral contraceptives) until three months after termination of treatment
• a maximum of eight chemotherapy cycles prior to registration (CR/ PR/ MR/ or PD)

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 the time of registration
• Preceding autologous stem cell transplantation
• age > 61 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Auto-Allo Tandem Stem cell Transplantation plus maintenance therapy with Thalidomide and DLI	Procedure: Auto-Allo Tandem SCT and maintenance therapy with Thalidomide/ DLI; *Multiple myeloma; -> Induction Therapy (max. 8 cycles); -> Registration of patient, stem cell mobilization, start of donor search; -> Melphalan (200mg/qm) plus autologous PBSCT; -> 2 months later: Melphalan plus allogeneic PBSCT; -> day 120 after allogeneic PBSCT: Thalidomide, 100mg (max. 2 years or until progress or non-tolerable toxicity, respectively); -> day 180 after allogeneic PBSCT (if CsA discontinued): First DLI (1 x 10^6 (MRD) or 5 x 10^5 (MUD) CD3+ cells per kg BW); -> day 250 after allogeneic PBSCT: second DLI (if no signs of GvHD: dose escalation by 0,5 Log); -> Day 320 after allogeneic PBSCT: Third DLI (if no signs of GvHD: dose escalation by 0,5 Log); -> Further DLI depending on MRD-measurement
Active Comparator: B; Auto-Auto Tandem stem cell Transplantation plus maintenance therapy with Thalidomide	Procedure: auto-auto Tandem stem cell transplantation and maintenance therapy with Thalidomide; *Multiple myeloma; -> Induction Therapy (max. 8 cycles); -> Registration of patient, stem cell mobilization, start of donor search; -> Melphalan (200mg/qm) plus autologous PBSCT; -> if no donor available (max 4 weeks after autologous PBSCT) or if patients declines allogeneic PBSCT): 2 months: Melphalan (200mg/qm) plus autologous PBSCT; -> day 120 after autologous PBSCT: Thalidomide, 100mg (max. 2 years or until progress or non-tolerable toxicity, respectively)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival 4 years after auto-allo/ auto-auto Tandem-SCT. Any of the following will be considered an endpoint event: recurrence or progression of primary disease, disease related mortality, or treatment related mortality.	four years after Tandem stem cell transplantation

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of acute GvHD	day +100 after allogeneic stem cell transplantation
Incidence of chronic GvHD	at one year and at two years after allogeneic stem cell transplantation
Toxicity of conditioning regimen and of maintenance therapy	Throughout conditioning regimen and maintenance therapy
cumulative incidence of relapse	four years after Tandem stem cell transplantation
Disease related mortality	four years after allogeneic stem cell transplantation
Treatment related mortality	four years after allogeneic stem cell transplantation
overall survival	four years after allogeneic stem cell transplantation

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Nicolaus Kroeger, Prof. Dr., University Medical Center Hamburg-Eppendorf, Department for Stem Cell Transplantation

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2008
• Primary Completion (Actual): April 17, 2018
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: October 22, 2008
• First Submitted That Met QC Criteria: October 22, 2008
• First Posted (Estimated): October 23, 2008

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Thalidomide; Multiple Myeloma; Stem Cell Transplantation; DLI
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Trace Elements; Micronutrients; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide; Ferrous fumarate
• Other Study ID Numbers: Auto-Allo TSCT in MM