Clinical trial NCT01090089: Combination of Lenalidomide and Dexamethasone in Treatment of Multiple Myeloma
Official title: The Combination of Lenalidomide and Dexamethasone With or Without Intensification by High-dose Melphalan in the Treatment of Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
Sponsor class: OTHER
Collaborators: name: ClinAssess GmbH
First posted: 2010-03-19
Enrollment: 348
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study for elderly myeloma patients lenalidomide plus low-dose dexamethasone until progression is being compared with age-adjusted tandem high-dose melphalan 140 mg/m² augmented by induction with 3 cycles of lenalidomide plus low-dose dexamethasone before transplantation and lenalidomide maintenance after transplantation.


Eligibility criteria: Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form. 2. Age 60-75 years at the time of signing the informed consent form. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Symptomatic MM requiring therapy. 5. Measurable monoclonal protein in serum and/or urine 6. Monoclonal plasma cells in the bone marrow \>/= 10% and/or biopsy-proven plasmacytoma 7. Myeloma-related organ dysfunction, at least one of \[C\] Calcium elevation in the serum (\> 11.5 mg/dL or \> 2.65 mmol/l) \[R\] Renal insufficiency (creatinine \> 173 μmol/l or \> 2 mg/dL) \[A\] Anemia (Hb \< 10 g/dL or 2 g/dL \< normal) \[B\] Bone lesions or general osteoporosis 8. ECOG PS of \</= 2 ... 9. Laboratory test results within these ranges within 1 week prior to randomization:

* ANC \>/= 1.0 x 109/L.
* Platelet count \>/= 75 x 109/L or in case of bone marrow infiltration with myeloma cells \>/= 30 x 109/L.
* Total bilirubin \</= 2 mg/dL.
* AST (SGOT) and ALT (SGPT) \</= 3 x ULN. 8. Female subjects of childbearing potential must: o Understand the study drug is expected to have a teratogenic risk

  o Agree to use, ..., effective contraception without interruption,...

  o Understand that even if she has amenorrhea, she must follow all the advice on effective contraception.

  o She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy

  o Agree to have a medically supervised pregnancy test ...
* Male subjects must

  o Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study drug therapy ...
  * Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
* All subjects must

  * Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
  * Agree not to share study drug with another person and to return all unused study drug to the investigator.

    9. Disease free of prior malignancies for \>/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

    10. Able to receive antithrombotic prophylaxis (...). 11. Life-expectancy \> 3 months.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF.
2. Pregnant or lactating females
3. Any condition, incl. the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Patient currently is enrolled in another clinical research study or has been enrolled ...within 4 weeks before randomization and/or is receiving an investigational agent for any reason ...
5. Known hypersensitivity to thalidomide, dexamethasone, or melphalan.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Any prior use of lenalidomide.
8. Concurrent use of other anti-cancer agents or treatments.
9. Known positive for HIV or active infectious hepatitis, type A, B or C or treponema pallidum
10. Prior treatment with dexamethasone discontinued because of ≥ grade 3 dexamethasone-related toxicity.
11. Any prior chemotherapy with the exception of a short course of dexamethasone more than 4 weeks before randomization.
12. Immunotherapy or antibody therapy within 8 weeks before randomization.
13. Major surgery within 4 weeks before randomization.
14. Renal failure requiring dialysis.
15. Myocardial infarction within 6 months before randomization, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
16. Severe pulmonary disease (diffusion capacity \< 60% of normal).
17. Treatment for cancer other than MM within 5 years before randomization, with the exception of basal cell carcinoma or cervical cancer in situ.
18. Cardiac amyloidosis.
19. Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to the protocol.
20. Any systemic infection requiring treatment.
21. Unability or unwillingness of the patient to receive antithrombotic prophylaxis.

    -

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 5 yrs
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 yrs
measure: • Response (complete response [CR], stringent complete response [sCR], very good partial response [VGPR], partial response [PR] and overall response [CR (incl. sCR)+ VGPR + PR]) according to IMWG criteria
timeFrame: 5 yrs
Other outcomes:
Locations:
city: Muenster
country: Germany
facility: Universitätsklinikum Münster
state: North Rhein Westfallen
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Berg
country: Germany
facility: Agirov Klinik
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Bielefeld
country: Germany
facility: Evangelisches Krankenhaus Bielefeld
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Erlangen
country: Germany
facility: Universitätsklinik Erlangen
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Greifswald
country: Germany
facility: Universitätsklinikum der Ernst-Moritz-Arndt-Universität Greifswald -Anstalt öffentlichen Rechts-
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein gGmbH
city: Landshut
country: Germany
facility: Klinikum Landshut gemeinnützige GmbH
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwäbisch Gmünd
city: München
country: Germany
facility: Hämato-Onkologische Schwerpunktpraxis
city: München
country: Germany
facility: Onkologische Praxis Elisenhof
city: München
country: Germany
facility: Klinikum München Harlaching
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Nürnberg
country: Germany
facility: Klinikum Nord
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann gGmbH
city: Ravensburg
country: Germany
facility: Gemeinschaftspraxis für Innere Medizin, Hämatologie und Onkologie
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
city: Stuttgart
country: Germany
facility: Diakonie-Klinikum Stuttgart-Diakonissenkrankenhaus und Paulinenhilfe gGmbH
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Traunstein
country: Germany
facility: Klinikum Traunstein
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wiesbaden
country: Germany
facility: HSK Dr. Horst-Schmidt-Kliniken gmbh
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
Study officials:
affiliation: Agirov Klinik
name: Christian Straka
role: PRINCIPAL_INVESTIGATOR
References: