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Multiple MyelomaPhase 3DSMM-IINCT02288741

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

A Phase 3 study testing Anthracycline/dexamethasone-based induction chemotherapy, Tumor-reduction chemotherapy and stem cell mobilization and Stem cell apheresis in people with Multiple Myeloma, run by WiSP Wissenschaftlicher Service Pharma GmbH.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 60 to 70 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Anthracycline/dexamethasone-based induction chemotherapy, Tumor-reduction chemotherapy and stem cell mobilization and Stem cell apheresis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
549 participants
Where
No sites listed yet
Study dates
Aug 2001to Sep 2012
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 16Show fewer
  • 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

About this study

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

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.

Read the 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.

Being tested
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)
Keywords
high-dose chemotherapy, autologous blood stem-cell transplantation, induction chemotherapy, elderly patients
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anthracycline/dexamethasone-based induction chemotherapyDrug

    Also called ID, VAD, CAD

    4 cycles of anthracycline/dexamethasone-based chemotherapy

  • Dexamethasone for control of symptomsDrug

    Also called dexamethasone

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

  • Tumor-reduction chemotherapy and stem cell mobilizationDrug

    Also called IEV + G-CSF

    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)

  • Stem cell apheresisProcedure or surgery

    Also called SC-apheresis

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

  • Tandem high-dose chemotherapy (melphalan)Drug

    Also called Tandem melphalan

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

  • Autologous peripheral blood stem cell transplantationProcedure or surgery

    Also called PBSCT

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

Study groups in NCT02288741
Study groupRoleWhat they receive
A1: Induction chemotherapyExperimentalAnthracycline/dexamethasone-based induction chemotherapy Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
Receives: 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 chemotherapyActive comparatorDexamethasone for control of symptoms Tumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
Receives: 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: ObservationOtherTumor-reduction chemotherapy and stem cell mobilization Stem cell apheresis Tandem high-dose chemotherapy Autologous peripheral blood stem cell transplantation
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event free survival

    Calculated according to the method of Kaplan and Meier

    Measured: From randomization to 10 years follow up

Secondary outcomes (5)

  1. Overall survival

    Calculated according to the method of Kaplan and Meier

    Measured: From randomization to 10 years follow up

  2. 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.

    Measured: After last therapy to at least 6 weeks thereafter

  3. 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.

    Measured: After last therapy to at least 6 weeks thereafter

  4. 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)

    Measured: From randomization until 2 years after last therapy

  5. 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.

    Measured: From randomization to 10 years follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2014 (estimated)
  2. Study startAug 2001
  3. Primary completionSep 2012
  4. Study completionSep 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
549 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02288741
Sponsor's protocol ID
WiSP_AM71
Other IDs
protocol version 08/01/2001
Acronym
DSMM-II
Status last verified
Nov 2014
First submitted
23 Oct 2014
Last updated
11 Nov 2014
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 9753033

  • 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.

    PubMed 2301376

  • 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.

    PubMed 12028028

  • 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.

    PubMed 14586157

  • 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.

    PubMed 11249035

  • 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.

    PubMed 27662018

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Anthracycline/dexamethasone-based induction chemotherapy, Tumor-reduction chemotherapy and stem cell mobilization and Stem cell apheresis in people with Multiple Myeloma, run by WiSP Wissenschaftlicher Service Pharma GmbH.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event free survival (time frame: From randomization to 10 years follow up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02288741, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2014.

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