Trial Title:
Use of Thalidomide, Lenalidomide, Carfilzomib, Bortezomib and Vorinostat in the Initial Treatment of Newly Diagnosed Multiple Myeloma Patients
NCT ID:
NCT01554852
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Thalidomide
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
Melphalan
Lenalidomide
Bortezomib
Vorinostat
BB 1101
Conditions: Keywords:
myeloma
lenalidomide
Revlimid
cyclophosphamide
dexamethasone
bortezomib
Velcade
vorinostat
Zolinza
stem cell
carfilzomib
Kyprolis
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Unknown status
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Induction (intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone (CRD) regimen
Description:
Days 1 & 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4
& 12-15 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days
Arm group label:
Intensive pathway
Other name:
Revlimid (lenalidomide)
Intervention type:
Drug
Intervention name:
Induction (intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone (CTD) regimen
Description:
Days 1,8,15 (i.e. weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg
hard capsules. Initially 100 mg daily PO for 3 weeks, increasing to 200 mg daily PO Days
1-4 and 12-15 - dexamethasone 40 mg daily PO The cycle is repeated every 21 days
Arm group label:
Intensive pathway
Intervention type:
Drug
Intervention name:
Induction (intensive pathway) - carfilzomib, cyclophosphamide, lenalidomide, & dexamethasone (CCRD) regimen
Description:
Days 1 & 8 - cyclophosphamide 500 mg PO Days 1 & 2, 8 & 9, 15 & 16 - carfilzomib 20*/36
mg/m2** IV (*carfilzomib 20 mg/m2 is only administered on days 1 and 2 of cycle 1;
**carfilzomib will be dose capped at a body surface area of 2.2 m2) Days 1-21 -
lenalidomide 25 mg daily PO Days 1-4, 8, 9 & 15, 16 - dexamethasone 40 mg daily PO This
cycle is repeated every 28 days
Arm group label:
Intensive pathway
Other name:
Kyprolis (carfilzomib)
Other name:
Revlimid (lenalidomide)
Intervention type:
Drug
Intervention name:
Induction (non-intensive pathway) - cyclophosphamide, lenalidomide, & dexamethasone attenuated (CRDa) regimen
Description:
Days 1 & 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4
& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days
Arm group label:
Non-intensive pathway
Other name:
Revlimid (lenalidomide)
Intervention type:
Drug
Intervention name:
Induction (non-intensive pathway) - cyclophosphamide, thalidomide, & dexamethasone attenuated (CTDa) regimen
Description:
Days 1, 8, 15, 22 (weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg
hard capsules; initially 50 mg daily PO for 4 weeks, increasing every 4 weeks by 50 mg
increments to 200 mg daily PO Days 1-4 & 15-18 - dexamethasone 20 mg daily PO This cycle
is repeated every 28 days
Arm group label:
Non-intensive pathway
Intervention type:
Drug
Intervention name:
Consolidation (intensive & non-intensive pathways) - bortezomib, cyclophosphamide, & dexamethasone (VCD) regimen
Description:
Days 1, 4, 8 & 11 - bortezomib 1.3 mg/m2 SC or IV Days 1, 8, 15 - cyclophosphamide 500 mg
PO Days 1-2, 4-5, 8-9 & 11-12 - dexamethasone 20 mg daily PO This cycle is repeated every
21 days
Arm group label:
Intensive pathway
Arm group label:
Non-intensive pathway
Other name:
Velcade (bortezomib)
Intervention type:
Drug
Intervention name:
Maintenance (intensive & non-intensive pathways) - lenalidomide maintenance
Description:
Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days
Arm group label:
Intensive pathway
Arm group label:
Non-intensive pathway
Other name:
Revlimid (lenalidomide)
Intervention type:
Drug
Intervention name:
Maintenance (intensive & non-intensive pathways - protocol v5.0 only) - lenalidomide plus vorinostat maintenance
Description:
Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 & 15-21 - vorinostat 300mg PO This cycle
is repeated every 28 days
Arm group label:
Intensive pathway
Arm group label:
Non-intensive pathway
Other name:
Revlimid (lenalidomide)
Other name:
Zolinza (vorinostat)
Intervention type:
Drug
Intervention name:
High dose melphalan therapy and autologous stem cell transplant (intensive pathway only)
Description:
High dose melphalan therapy and autologous stem cell transplant to be given as per local
practice
Arm group label:
Intensive pathway
Summary:
The purpose of this study is to compare a standard chemotherapy regimen of
cyclophosphamide, dexamethasone plus thalidomide with a newer regimen of
cyclophosphamide, dexamethasone plus lenalidomide with or without carfilzomib.
Patients who do not have the best response to their initial treatment may then also be
given a combination of cyclophosphamide, dexamethasone plus bortezomib.
Patients who are relatively fit may, on their doctor's advice, go on to receive more
intensive chemotherapy, supported with a transplant of their own blood cells. This is
standard treatment which patients may be offered anyway even if they didn't take part in
this study.
After maximal response has been achieved with the treatment described above, and as long
as the myeloma has not got worse, patients will be treated with either long-term
lenalidomide, lenalidomide with vorinostat, or receive no further treatment, with close
observation.
Detailed description:
The last ten years has seen the introduction of a number of effective new anti-myeloma
agents into the clinical arena. These agents have been shown to be highly effective in
the relapse setting and now are being introduced as treatment earlier in the disease
course.
This study aims to address in the randomised setting some of the key questions concerning
the use of thalidomide, bortezomib, lenalidomide, carfilzomib and vorinostat in the
initial treatment of multiple myeloma patients.
Newly diagnosed patients of all ages with symptomatic myeloma requiring treatment are
eligible.
For initial treatment, thalidomide in combination with cyclophosphamide and
dexamethasone, the UK gold standard, will be compared with the newer combination of
lenalidomide, cyclophosphamide and dexamethasone with or without carfilzomib.
For patients with a sub-optimal response to initial therapy, the response to the
proteasome inhibitor bortezomib will be assessed, as previous studies have demonstrated
that it is able to induce responses and improve progression-free and overall survival in
patients resistant to standard chemotherapy. Patients young and fit enough to tolerate an
autologous transplant will then proceed to high dose melphalan with peripheral blood stem
cell rescue and then on to maintenance randomisation. Older or less fit patients will go
directly to a maintenance randomisation.
The value of lenalidomide and lenalidomide combined with vorinostat maintenance will then
be assessed by randomising eligible patients to receive either lenalidomide, lenalidomide
combined with vorinostat maintenance therapy, or close observation.
The primary end points of the study are overall and progression-free survival (OS and
PFS). Secondary end points include response and toxicity.
A number of laboratory based studies will also be performed in order to determine patient
specific factors predicting overall and progression-free survival and response to
treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Aged 18 years or greater
- Newly diagnosed as having symptomatic multiple myeloma or non-secretory multiple
myeloma
- Provide written informed consent
- Women of childbearing potential and male patients whose partner is a woman of child
bearing potential must be prepared to use contraception in accordance with (and
consent to) the Celgene-approved process for thalidomide and lenalidomide Risk
Management and Pregnancy Prevention, or commit to absolute and continuous abstinence
- Women of child bearing potential must have a negative pregnancy test performed by a
healthcare professional in accordance with the Celgene-approved process for
thalidomide and lenalidomide Risk Management and Pregnancy Prevention
Exclusion Criteria:
- Asymptomatic myeloma
- Solitary plasmacytoma of bone. (Patients with previous solitary plasmacytoma now
progressed to symptomatic or non-secretory myeloma are eligible)
- Extramedullary plasmacytoma (without evidence of myeloma)
- Previous (<5 years since diagnosis) or concurrent active malignancies, except
surgically-removed basal or squamous cell carcinoma of the skin, treated carcinoma
in situ of the breast or cervix, or incidental histologic finding of prostate cancer
(TMN stage of T1a or 1b). Patients with remote histories (>5 years) of other cured
malignancies may be entered.
- Documented diagnosis of Myelodysplastic Syndrome (MDS) that meets International
Prognostic Scoring System (IPSS) criteria for high-risk disease
- Previous treatment for myeloma, except the following: local radiotherapy to relieve
bone pain or spinal cord compression; or prior bisphosphonate treatment; or
corticosteroids within the last 3 months
- Known history of allergy contributable to compounds containing boron or mannitol
- Grade 2 or greater (NCI criteria) peripheral neuropathy
- Acute renal failure (unresponsive to up to 72 hours of rehydration, characterised by
creatinine >500µmol/L or urine output <400 mL/day or requirement for dialysis)
- Lactating or breastfeeding
- Patient has active or prior hepatitis C
- Caution is advised in patients with a past history of ischaemic heart disease,
pericardial disease, acute diffuse infiltrative pulmonary disease or psychiatric
disorders, evidence of impaired marrow function or elevated liver function tests,
but exclusion is essentially to be at the discretion of the treating clinician
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
112 sites UK wide
Address:
City:
United Kingdom
Country:
United Kingdom
Start date:
May 2010
Completion date:
December 2022
Lead sponsor:
Agency:
University of Leeds
Agency class:
Other
Collaborator:
Agency:
Celgene
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Collaborator:
Agency:
Amgen
Agency class:
Industry
Source:
University of Leeds
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01554852
http://www.isrctn.com/ISRCTN49407852
http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-lenalidomide-bortezomib-intensive-treatment-group-myeloma-XI
http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-lenalidomide-bortezomib-myeloma-non-intensive-treatment-group-myeloma-XI
http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.8009
https://learningcenter.ehaweb.org/eha/2017/22nd/181694/charlotte.pawlyn.quadruplet.vs.sequential.triplet.induction.therapy.for.html
https://learningcenter.ehaweb.org/eha/2017/22nd/182068/charlotte.pawlyn.lenalidomide.induction.and.maintenance.therapy.for.transplant.html
http://www.nature.com/articles/bcj2016114
