enalidomide (Revlimid®), Adriamycin and Dexamethasone (RAD) as an Induction Therapy in Newly Diagnosed Multiple Myeloma Followed by a Risk-Defined Transplant Strategy and Lenalidomide Maintenance – A Multicenter Phase II Trial by Deutsche Studiengruppe Multiples Myelom
- Conditions
- Multiple MyelomaMedDRA version: 16.1Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864
- Registration Number
- EUCTR2008-000007-28-DE
- Lead Sponsor
- niversitaetsklinikum Wuerzburg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 190
Main Inclusion Criteria (for RAD)
1.Understand and voluntarily sign an informed consent form.
2.Age = 18 and <= 65 years at the time of signing the informed consent form.
3.Able to adhere to the study visit schedule and other protocol requirements.
4.Newly diagnosed multiple myeloma with the diagnostic criteria as follows:
- Monoclonal plasma cells in the bone marrow = 10% (histology) and/or biopsy-proven plasmacytoma
- Monoclonal protein present in serum and/or urine on immunofixation
- Myeloma-related organ dysfunction, at least one of
- [C] Calcium elevation in the serum (> 11.5 mg/dL or upper limit of normal)
- [R] Renal insufficiency (creatinine > 2 mg/dL)
- [A] Anemia (Hb < 10 g/dL or 2 g/dL < normal)
- [B] Bone lesions or general osteoporosis or
- symptomatic hyperviscosity or
- recurrent bacterial infection (= 2 per year)
and measurable disease parameters
- IgG myeloma: Serum monoclonal paraprotein (M-protein) level = 1.0 g/dL or urine M-protein level = 200 mg/24 hours or IgA myeloma: Serum M-protein level = 0.5 g/dL or urine M-protein level = 200 mg/24 hours or IgD myeloma: Serum M-protein level = 0.05 g/dL or urine M-protein level = 200 mg/24 hours or Light chain myeloma: Serum M-protein level = 1.0 g/dL or urine M protein level = 200 mg/24 hours
5. A maximum of two cycles of one prior anti-myeloma regimen excluding thalidomide (i.e., dexamethasone; AD; ID; VAD; VID; melphalan/prednisone).
6. Cardiac ejection fraction (LVEF) of at least 55% assessed by 2-d echocardiography within 28 days prior to first cycle of RAD
7. DLCO of at least 60% of age matched controls or if DLCO cannot be measured pO2 [art.] = 70 mm Hg as a substitute for DCLO
8. ECOG performance status of <= 2 at study entry (see Appendix III).
9. Laboratory test results within these ranges:
- Absolute neutrophil count = 1.5 x 10E9/L
- Platelet count = 75 x 10E9/L
- Calculated creatinine clearance = 50 mL/minute.
- Total bilirubin = 1.5 mg/dL
- AST (SGOT) and ALT (SGPT) <= 2 x ULN
10.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
11.Able to administer low molecular weight heparin (either enoxaparin 40 mg once daily or dalteparin 5.000 IU once daily) as a prophylactic anticoagulation therapy for the first six months following diagnosis/enrolment. If impaired renal function is present, measurement of anti-factor-Xa-activity must be performed.
12.Two cycles of any standard anti-myeloma chemotherapy, plasmapheresis for hyperviscosity and radiotherapy for symptomatic fractures or surgery for compression syndromes are allowed. Patients must not have progression on conventional cytotoxic pre-treatment.
13.Patients willing and able to undergo tandem-autologous and (if allocated to the autologous-allogeneic arm) allogeneic transplantation
14.Bone marrow sample available for assessment of cytogenetic factors by FISH analysis (centralized diagnostic laboratory)
Inclusion Criterias for a) autologous/allogeneic stem cell transplantation, b) Lenalidomide maintenance phase, c) Contraception see protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Progressive disease (PD) to any initial treatment, such as dexamethasone, dex-anthracycline combinations or melphalan/prednisone. Those patients are considered to have refractory disease, the treatment of which is not an endpoint of this protocol.
3. Pregnant or lactating females.
4. Any condition, including 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.
5. Use of any other experimental drug or experimental therapy within 28 days of baseline and for duration of the entire study.
6. Neuropathy of <= grade 2 severity
7. Known hypersensitivity to thalidomide.
8. The development of erythema nodosum; if characterized by a desquamating rash while taking thalidomide or similar drugs.
9. Any prior use of lenalidomide.
10. Positive for HIV or infectious hepatitis, type A, B or C or treponema pallidum after serologic testing
11. History of myocardial infarction (both STEMI and non-STEMI).
12. Concomitant myocarditis or perimyocarditis.
Exclusion criterion for second cycle of high-dose melphalan
13.The second cycle of high-dose melphalan must only be initiated if in addition to the planned graft a back up” of at least 2 x 106 CD34+ cells of the patient be present that may be used in case of graft failure.
Exclusion criteria for allogeneic stem cell transplantation
14. Serum creatinine despite induction therapy = 2.0 mg/dL
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine efficacy of the novel induction regimen (combination of lenalidomide, adriamycin, and dexamethasone; RAD) followed by a risk-defined transplant strategy and subsequent lenalidomide maintenance in patients with symptomatic multiple myeloma;Secondary Objective: To assess long-term efficacy and safety of the treatment regimen;Primary end point(s): Response rate (sCR, CR, or VGPR) at the start of scheduled lenalidomide maintenance<br><br>Secondary end point(s)<br>• Other efficacy parameters according to the international uniform response criteria, including objective response (sCR, CR, VGPR, or PR), progression-free (PFS) and overall survival (OS), and time to next anti-myeloma therapy<br>•Incidence of adverse events taking into account type, severity, and relationship to study treatment<br>
- Secondary Outcome Measures
Name Time Method