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

Sponsor

Universitätsklinikum Hamburg-Eppendorf (Other)

Overall Status

Unknown status

CT.gov ID

NCT00777998

Collaborator

(none)

221

Enrollment

Locations

Arms

115.5

Anticipated Duration (Months)

11.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Procedure: Auto-Allo Tandem SCT and maintenance therapy with Thalidomide/ DLI Procedure: auto-auto Tandem stem cell transplantation and maintenance therapy with Thalidomide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

221 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 14, 2008

Actual Primary Completion Date :

Apr 17, 2018

Anticipated Study Completion Date :

Jun 1, 2018

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Klinikum Augsburg	Augsburg	Germany	86156
2	Charité	Berlin	Germany	12203
3	Universitätsklinikum Dresden	Dresden	Germany	01307
4	Universitätsklinikum Düsseldorf	Düsseldorf	Germany	40225
5	Universitätsklinikum Erlangen	Erlangen	Germany	91054
6	Universitätsklinikum Essen	Essen	Germany	45122
7	Klinikum Frankfurt (Oder) GmbH	Frankfurt (Oder)	Germany	15236
8	Universitätsklinikum Greifswald	Greifswald	Germany	17475
9	Universitätsklinikum Göttingen	Göttingen	Germany	37075
10	Universitätsklinikum Halle (Saale)	Halle (Saale)	Germany	06097
11	University Medical Center Hamburg-Eppendorf	Hamburg	Germany	20246
12	Asklepios Klinik Altona	Hamburg	Germany	22763
13	Medizinische Hochschule Hannover	Hannover	Germany	30625
14	Universitätsklinikum Heidelberg	Heidelberg	Germany	69120
15	Universitätsklinikum Marburg	Marburg	Germany	35032
16	Universitätsklinikum Münster	Münster	Germany	48149
17	Robert-Bosch-Krankenhaus	Stuttgart	Germany	70376
18	Universitätsklinikum Tübingen	Tübingen	Germany	72076
19	Deutsche Klinik für Diagnostik	Wiesbaden	Germany	65191
20	Horst Schmidt Kliniken GmbH	Wiesbaden	Germany	65199