enalidomide, Adriamycin, Dexamethasone (RAD)Versus Lenalidomide, Bortezomib, Dexamethasone (VRD) for Induction in Newly Diagnosed Multiple Myeloma followed by Response-adapted Consolidation and Lenalidomide Maintenance - A Randomized Multicenter Phase III Trial by Deutsche Studiengruppe Multiples Myelom (DSMM XIV)
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-016616-21-DE
- Lead Sponsor
- Wuerzburg University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 470
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. Eligible for autologous and allogeneic stem cell Transplantation
4. Must not have been previously treated with any prior systemic therapy for the treatment of multiple
myeloma (dexamethasone at a cumulative dose of 320 mg; plasmapheresis/dialysis without concomitant chemotherapy, local irradiation of bone lesions; and surgical intervention is accepted
as pretreatment)
5. 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 eneral osteoporosis
or
symptomatic hyperviscosity or ecurrent acterial infection (= 2 per year) and measurable disease parameters as follows:
- Serum monoclonal paraprotein (M-component) level = 1 g/dL and/or urine Mprotein level = 200 mg/24 hours
- In case of IgA myeloma: Serum monoclonal paraprotein level = 0.5 g/dL and/or urine M-protein level = 200 g/24 hours.
- For patients with no detectable M-component:
Serum FLC assay: Involved FLC level > 10 mg/dl (> 100 mg/l) provided serum FLC ratio is abnormal.
6. Cardiac ejection fraction (LVEF) of at least 50% assessed by 2-d echocardiography within 28 days
prior to first cycle of RAD or VRD
7. Corrected DLCO (single breath) of at least 50% of age-matched controls; alternatively pO2 [art.] of
at least 70 mmHg
8. Karnofsky performance status of greater or equal to 50% (see Appendix III)
9. Laboratory test results within these ranges:
• Absolute neutrophil count = 1.0 x 109/L
• Platelet count = 75 x 109/L
• Hemoglobin > 8 g/dL
• Calculated creatinine clearance (MDRD) = 30 mL/Minute
• Total bilirubin < 1.5 x ULN
• AST and ALT < 2.5 x ULN
• Corrected serum calcium level < 3.5 mmol/l (< 4 mg/dl)
10. Pregnancy prevention plan for all females, females with childbearing (FCBP) potential, females not of childbearing potential, male subjects and all subjects. For Details please see chapter 5.3.2.1 (inclusion criteria) of protocol Version 9.0 (29.09.2017).
11. Bone marrow sample available for analysis of molecular cytogenetics (Lab Dr. Langer, Ulm).
12. 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 three months following
diagnosis/enrolment (applicable for subjects randomized to RAD) and able to administer ASS 100
mg/d (applicable for subjects randomized to VRD). If impaired renal function is present,
measurement of anti-factor-Xa-activity must be performed.
13. Patients willing and able to undergo autologous and allogeneic transplantation
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. Pregnant or lactating females
3. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk
4. History of myocardial infarction; NYHA Class III or IV heart failure, uncontrolled
angina, severe uncontrolled ventricular arrhythmias; concomitant pericarditis or peri-
/myocarditis
5. Use of any other experimental drug or therapy within 28 days of baseline.
6. Greater or equal to Grade 2 peripheral neuropathy on clinical examination within 14
days before enrollment
7. Known intolerance of boron
8. Hypersensitivity to acyclovir or similar anti-viral drug
9. Prior malignancy
10. HIV positive, active hepatitis B, C or D viral infection, known CMV reactivation/active
infection, EBV reactivation/active infection or treponema pallidum infection
11. Uncontrolled diabetes mellitus
12. Non-secretory MM
13. Clinically relevant active infection or serious co-morbid medical conditions
14. Cardiac amyloidosis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare CR rate to two induction regimens (one novel agent [RAD] vs. two novel agents [VRD]) in newly diagnosed MM patients and to determine PFS following consolidative treatment.;Secondary Objective: To assess long-term efficacy and safety of the treatment regimen.<br>To assess quality of life in terms of frequency and duration of hospitalization as well as toxicity during different means of consolidation .<br>;Primary end point(s): The primary efficacy endpoint for the induction phase is CR rate at first restaging<br>In the consolidation phase the primary efficacy endpoint for comparison II (response < VGPR after first ASCT) is the PFS rate at 3 years after the first ASCT, calculated from day 1 of ASCT.<br>In comparison I (response = VGPR after first ASCT), PFS will be compared only exploratively in addition to toxicity and quality of life (in terms of frequency and duration of hospital stays).<br>;Timepoint(s) of evaluation of this end point: first Restaging and 3 years after first ASCT
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ORR rate following 3 cycles of induction treatment (VRD vs RAD )<br>CR and ORR at the end of the whole treatment programme<br>Overall survival<br>Incidence, severity and relationship of SAEs<br>Numbers of hospital stays and hospitalization days within two years from second restaging.<br>;Timepoint(s) of evaluation of this end point: first Restaging and end of treatment