Back to results

Tandem Melphalan and Autolog. SCT in MM Patients 60 to 70 Years of Age With and Without Induction Chemotherapy (DSMM-II)

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Anthracycline/dexamethasone-based induction chemotherapy

Dexamethasone for control of symptoms

Tumor-reduction chemotherapy and stem cell mobilization

Stem cell apheresis

Tandem high-dose chemotherapy (melphalan)

Autologous peripheral blood stem cell transplantation

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring high-dose chemotherapy, autologous blood stem-cell transplantation, induction chemotherapy, elderly patients

Eligibility Criteria

60 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histological confirmed multiple myeloma stage II or III according to the classification of Salmon and Durie
Aged between 60 and 70 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Signed and dated written informed consent
No previous chemotherapy or not more than one cycle in total or previous chemotherapy of more than one cycle if paused for at least 6 months and not more than six cycles in total (arm A1 and A2 only)
Ongoing primary chemotherapy of two to maximum six cycles (arm B only)

Exclusion Criteria:

Multiple myeloma stage I according to the classification of Salmon and Durie without need of any therapy
Aged under 60 or over 70 years
ECOG performance status >2
Previous chemotherapy of more than six cycles
Informed consent missing
Myocardial infarction within the last six months
Cardiac dysrhythmia stage IV b according to the classification of Lown
Heart failure >NYHA II according to the classification of the New York Heart Association (NYHA), left ventricular ejection fraction <50% in ECG
Severe restrictive or obstructive pulmonary disease (diffusing capacity <60% under normal)
Renal insufficiency including a serum creatinine level >2mg/dl if not caused by multiple myeloma and reversible
Liver diseases combined with an elevation of transaminases and of bilirubin of three times above normal
Severe infections (HIV, hepatitis B/C, syphilis etc. )
Severe psychiatric disease
Other not curative treated malignant tumor within the last five years
Concurrent participation in other clinical studies
Other not curative treated malignant tumor within the last five years

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Other

Arm Label

A1: Induction chemotherapy

A2: No induction chemotherapy

B: Observation

Arm Description

Anthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation

Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation

Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation

Outcomes

Primary Outcome Measures

Event free survival

Calculated according to the method of Kaplan and Meier

Secondary Outcome Measures

Overall survival

Calculated according to the method of Kaplan and Meier

Rate of remission (Evaluation of the overall response rate)

Evaluation of the overall response rate. Overall repose is defined as complete response + partial response. The definition of remission followed the criteria of Bladé.

Quality of remission (Evaluation of the best response)

Evaluation of the best response. Response is evaluated after induction therapy, tumor-reduction chemotherapy and stem cell mobilization and each high-dose chemotherapy. The definition of remission followed the criteria of Bladé.

Short and long time toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE)

Examination of the maximum grade of toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE)

Cytogenetic examination (Univariate analysis according to the method of Kaplan and Meier. Multivariate analysis according to the method of Cox´s proportional hazards regression analysis.)

Examination of cytogenetic abnormalities wich are of major importance to define longer or shorter survival. Univariate analysis according to the method of Kaplan and Meier. Multivariate analysis according to the method of Cox´s proportional hazards regression analysis.

Full Information

NCT ID

NCT02288741

First Posted

October 23, 2014

Last Updated

November 6, 2014

Sponsor

WiSP Wissenschaftlicher Service Pharma GmbH

1. Study Identification

Unique Protocol Identification Number

NCT02288741

Brief Title

Tandem Melphalan and Autolog. SCT in MM Patients 60 to 70 Years of Age With and Without Induction Chemotherapy

Acronym

DSMM-II

Official Title

Phase III-study for Evaluation of Induction Therapy Before Stem Cell Mobilization and Tandem High-dose Melphalan in Multiple Myeloma Patients 60 to 70 Years of Age

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

August 2001 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

WiSP Wissenschaftlicher Service Pharma GmbH

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Patients 60 to 70 years of age with newly diagnosed multiple myeloma were prospectively randomized between 4 cycles of anthracycline/dexamethasone-based induction chemotherapy (A1) or only 2 x 4 days of dexamethasone (A2). A reference arm included patients who could not be randomized (B). Tandem melphalan 140 mg/m² (MEL140) with autologous transplantation was scheduled for all patients.

Detailed Description

In arm A1, patients received 4 cycles of conventional induction therapy with anthracycline/dexamethasone-based regimens. Specified in the protocol were vincristine/doxorubicin/dexamethasone (VAD), idarubicin/dexamethasone (ID) and cyclophosphamide/doxorubicin/dexamethasone (CAD). In arm A2, patients were planned to receive only dexamethasone 40 mg orally on days 1-4 and 8-11 for symptom control before stem cell mobilization. For the patients in arm B, a maximum of 6 cycles of induction chemotherapy was allowed. Following this, the treatment was identical for all patients. For stem cell mobilization, an age-adjusted IEV-regimen with granulocyte-colony stimulating factor (G-CSF) was recommended. The target dose for stem cell collection was 6 x 10E+6 CD34 (cluster of differentiation 34)-positive cells/kg (2 transplants and one back-up). The standard dose for each transplantation was 2 x 10E+6 CD34-positive cells/kg. High-dose melphalan at a total dose of 140 mg/m² (MEL140) was given in two doses of 70 mg/m² on days -3 and -2. Stem cell transplantation (SCT) was performed on day 0. A second MEL140 course was planned two months after the first. Regular bisphosphonate treatment was recommended.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

high-dose chemotherapy, autologous blood stem-cell transplantation, induction chemotherapy, elderly patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

549 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A1: Induction chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

A2: No induction chemotherapy

Arm Type

Active Comparator

Arm Description

Dexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation

Arm Title

B: Observation

Arm Type

Other

Arm Description

Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation

Intervention Type

Drug

Intervention Name(s)

Anthracycline/dexamethasone-based induction chemotherapy

Other Intervention Name(s)

ID, VAD, CAD

Intervention Description

4 cycles of anthracycline/dexamethasone-based chemotherapy

Intervention Type

Drug

Intervention Name(s)

Dexamethasone for control of symptoms

Other Intervention Name(s)

dexamethasone

Intervention Description

2 x 4 days of dexamethasone (day 1-4 and day 8-11: 40mg)

Intervention Type

Drug

Intervention Name(s)

Tumor-reduction chemotherapy and stem cell mobilization

Other Intervention Name(s)

IEV + G-CSF

Intervention Description

Ifosfamide (day 1-3: 1.900mg/m² iv), epirubicin (day 1: 75 mg/m² iv), etoposide (day 1-3: 120 mg/m² iv) and G-CSF (day 5 until end of apheresis: 5µg/kg sc)

Intervention Type

Procedure

Intervention Name(s)

Stem cell apheresis

Other Intervention Name(s)

SC-apheresis

Intervention Description

stem cell apheresis in peripheral blood, sought amount of CD34-cells: 6 * 10E6/kg

Intervention Type

Drug

Intervention Name(s)

Tandem high-dose chemotherapy (melphalan)

Other Intervention Name(s)

Tandem melphalan

Intervention Description

Two cycles of high-dose melphalan (day -3 and day -2: 70mg/m²)

Intervention Type

Procedure

Intervention Name(s)

Autologous peripheral blood stem cell transplantation

Other Intervention Name(s)

PBSCT

Intervention Description

Two infusions of collected stem cells (day 0: 2*10E6 CD34-cell/kg per transplantation)

Primary Outcome Measure Information:

Title

Event free survival

Description

Calculated according to the method of Kaplan and Meier

Time Frame

From randomization to 10 years follow up

Secondary Outcome Measure Information:

Title

Overall survival

Description

Calculated according to the method of Kaplan and Meier

Time Frame

From randomization to 10 years follow up

Title

Rate of remission (Evaluation of the overall response rate)

Description

Evaluation of the overall response rate. Overall repose is defined as complete response + partial response. The definition of remission followed the criteria of Bladé.

Time Frame

After last therapy to at least 6 weeks thereafter

Title

Quality of remission (Evaluation of the best response)

Description

Time Frame

After last therapy to at least 6 weeks thereafter

Title

Short and long time toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE)

Description

Examination of the maximum grade of toxicity according to NCI Common Terminology Criteria for Adverse Events (CTCAE)

Time Frame

From randomization until 2 years after last therapy

Title

Cytogenetic examination (Univariate analysis according to the method of Kaplan and Meier. Multivariate analysis according to the method of Cox´s proportional hazards regression analysis.)

Description

Time Frame

From randomization to 10 years follow up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histological confirmed multiple myeloma stage II or III according to the classification of Salmon and Durie Aged between 60 and 70 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Signed and dated written informed consent No previous chemotherapy or not more than one cycle in total or previous chemotherapy of more than one cycle if paused for at least 6 months and not more than six cycles in total (arm A1 and A2 only) Ongoing primary chemotherapy of two to maximum six cycles (arm B only) Exclusion Criteria: Multiple myeloma stage I according to the classification of Salmon and Durie without need of any therapy Aged under 60 or over 70 years ECOG performance status >2 Previous chemotherapy of more than six cycles Informed consent missing Myocardial infarction within the last six months Cardiac dysrhythmia stage IV b according to the classification of Lown Heart failure >NYHA II according to the classification of the New York Heart Association (NYHA), left ventricular ejection fraction <50% in ECG Severe restrictive or obstructive pulmonary disease (diffusing capacity <60% under normal) Renal insufficiency including a serum creatinine level >2mg/dl if not caused by multiple myeloma and reversible Liver diseases combined with an elevation of transaminases and of bilirubin of three times above normal Severe infections (HIV, hepatitis B/C, syphilis etc. ) Severe psychiatric disease Other not curative treated malignant tumor within the last five years Concurrent participation in other clinical studies Other not curative treated malignant tumor within the last five years

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christian Straka, Prof. Dr.

Organizational Affiliation

Schön Klink Starnberger See

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

9753033

Citation

Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. doi: 10.1046/j.1365-2141.1998.00930.x. No abstract available.

Results Reference

background

PubMed Identifier

2301376

Citation

Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203.

Results Reference

background

PubMed Identifier

12028028

Citation

Clark AD, Douglas KW, Mitchell LD, McQuaker IG, Parker AN, Tansey PJ, Franklin IM, Cook G. Dose escalation therapy in previously untreated patients with multiple myeloma following Z-Dex induction treatment. Br J Haematol. 2002 Jun;117(3):605-12. doi: 10.1046/j.1365-2141.2002.03519.x. Erratum In: Br J Haematol 2002 Sep;118(4):1201.

Results Reference

background

PubMed Identifier

14586157

Citation

Straka C, Hebart H, Adler-Reichel S, Werding N, Emmerich B, Einsele H. Blood stem cell collections after mobilization with combination chemotherapy containing ifosfamide followed by G-CSF in multiple myeloma. Oncology. 2003;65 Suppl 2:94-8. doi: 10.1159/000073368.

Results Reference

background

PubMed Identifier

11249035

Citation

Szelenyi H, Kreuser ED, Keilholz U, Menssen HD, Keitel-Wittig C, Siehl J, Knauf W, Thiel E. Cyclophosphamide, adriamycin and dexamethasone (CAD) is a highly effective therapy for patients with advanced multiple myeloma. Ann Oncol. 2001 Jan;12(1):105-8. doi: 10.1023/a:1008362107080.

Results Reference

background

PubMed Identifier

27662018

Citation

Straka C, Liebisch P, Salwender H, Hennemann B, Metzner B, Knop S, Adler-Reichel S, Gerecke C, Wandt H, Bentz M, Bruemmendorf TH, Hentrich M, Pfreundschuh M, Wolf HH, Sezer O, Bargou R, Jung W, Trumper L, Hertenstein B, Heidemann E, Bernhard H, Lang N, Frickhofen N, Hebart H, Schmidmaier R, Sandermann A, Dechow T, Reichle A, Schnabel B, Schafer-Eckart K, Langer C, Gramatzki M, Hinke A, Emmerich B, Einsele H. Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial. Haematologica. 2016 Nov;101(11):1398-1406. doi: 10.3324/haematol.2016.151860. Epub 2016 Aug 4.

Results Reference

derived

Learn more about this trial

Tandem Melphalan and Autolog. SCT in MM Patients 60 to 70 Years of Age With and Without Induction Chemotherapy

We'll reach out to this number within 24 hrs