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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Procedure: Auto-Allo Tandem SCT and maintenance therapy with Thalidomide/ DLI
* Procedure: auto-auto Tandem stem cell transplantation and maintenance therapy with Thalidomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Auto-Allo Tandem Stem cell Transplantation plus maintenance therapy with Thalidomide and DLI | Procedure: Auto-Allo Tandem SCT and maintenance therapy with Thalidomide/ DLI<br>* *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<br>|
| Active Comparator: B<br>Auto-Auto Tandem stem cell Transplantation plus maintenance therapy with Thalidomide | Procedure: auto-auto Tandem stem cell transplantation and maintenance therapy with Thalidomide<br>* *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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Stem Cell Transplantation, Thalidomide, DLI