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

NCT02288741 | Completed Phase 3

• 2 other identifiers: WiSP_AM71protocol version 08/01/2001
• Study Type: interventional
• Target: 549
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Event free survival

  Calculated according to the method of Kaplan and Meier

  From randomization to 10 years follow up

Secondary Outcomes (5)

• Overall survival

  From randomization to 10 years follow up

• Rate of remission (Evaluation of the overall response rate)

  After last therapy to at least 6 weeks thereafter

• Quality of remission (Evaluation of the best response)

  After last therapy to at least 6 weeks thereafter

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

  From randomization until 2 years after last therapy

• 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.)

  From randomization to 10 years follow up

Study Arms (3)

A1: Induction chemotherapy

EXPERIMENTAL

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

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

A2: No induction chemotherapy

ACTIVE COMPARATOR

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

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

B: Observation

OTHER

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

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

Interventions

Anthracycline/dexamethasone-based induction chemotherapy DRUG

4 cycles of anthracycline/dexamethasone-based chemotherapy

Also known as: ID, VAD, CAD

A1: Induction chemotherapy; B: Observation

Dexamethasone for control of symptoms DRUG

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

Also known as: dexamethasone

A2: No induction chemotherapy

Tumor-reduction chemotherapy and stem cell mobilization DRUG

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)

Also known as: IEV + G-CSF

A1: Induction chemotherapy; A2: No induction chemotherapy; B: Observation

Stem cell apheresis PROCEDURE

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

Also known as: SC-apheresis

A1: Induction chemotherapy; A2: No induction chemotherapy; B: Observation

Tandem high-dose chemotherapy (melphalan) DRUG

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

Also known as: Tandem melphalan

A1: Induction chemotherapy; A2: No induction chemotherapy; B: Observation

Autologous peripheral blood stem cell transplantation PROCEDURE

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

Also known as: PBSCT

A1: Induction chemotherapy; A2: No induction chemotherapy; B: Observation

Eligibility Criteria

• Age: 60 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• WiSP Wissenschaftlicher Service Pharma GmbH: lead

Related Publications (6)

• 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.

  PMID: 9753033 BACKGROUND

• 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.

  PMID: 2301376 BACKGROUND

• 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.

  PMID: 12028028 BACKGROUND

• 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.

  PMID: 14586157 BACKGROUND

• 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.

  PMID: 11249035 BACKGROUND

• 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.

  PMID: 27662018 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Anthracyclines; VAD I protocol; Dexamethasone; Hematopoietic Stem Cell Mobilization; Granulocyte Colony-Stimulating Factor; TANDEM (quinoxaline); Drug Therapy; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Biological Therapy; Therapeutics; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Christian Straka, Prof. Dr.

  Schön Klink Starnberger See

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: November 11, 2014
• Study Start: August 1, 2001
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 11, 2014

Record last verified: 2014-11