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

WiSP Wissenschaftlicher Service Pharma

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Procedure: Stem cell apheresis; Procedure: Autologous peripheral blood stem cell transplantation; Drug: Anthracycline/dexamethasone-based induction chemotherapy; Drug: Dexamethasone for control of symptoms; Drug: Tumor-reduction chemotherapy and stem cell mobilization; Drug: Tandem high-dose chemotherapy (melphalan)

Study type: Interventional

Funder types: Other

Identifiers

NCT02288741

WiSP_AM71

protocol version 08/01/2001 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 549 patients

Sex: All

Ages: 60 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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549 participants in 3 patient groups

A1: Induction chemotherapy

Experimental group

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

Treatment:

Drug: Tandem high-dose chemotherapy (melphalan)

Drug: Tumor-reduction chemotherapy and stem cell mobilization

Drug: Anthracycline/dexamethasone-based induction chemotherapy

Procedure: Autologous peripheral blood stem cell transplantation

Procedure: Stem cell apheresis

A2: No induction chemotherapy

Active Comparator group

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

Treatment:

Drug: Tandem high-dose chemotherapy (melphalan)

Drug: Tumor-reduction chemotherapy and stem cell mobilization

Drug: Dexamethasone for control of symptoms

Procedure: Autologous peripheral blood stem cell transplantation

Procedure: Stem cell apheresis

B: Observation

Other group

Description:

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

Treatment:

Drug: Tandem high-dose chemotherapy (melphalan)

Drug: Tumor-reduction chemotherapy and stem cell mobilization

Drug: Anthracycline/dexamethasone-based induction chemotherapy

Procedure: Autologous peripheral blood stem cell transplantation

Procedure: Stem cell apheresis