Trial record 3 of 1818 for:    myeloma

Use of Thalidomide, Lenalidomide, Bortezomib and Vorinostat in the Initial Treatment of Newly Diagnosed Multiple Myeloma Patients (Myeloma XI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by University of Leeds
Sponsor:
Collaborators:
Celgene Corporation
Merck Sharp & Dohme Corp.
Information provided by:
University of Leeds
ClinicalTrials.gov Identifier:
NCT01554852
First received: February 21, 2012
Last updated: March 19, 2012
Last verified: March 2012
  Purpose

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.

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.


Condition Intervention Phase
Multiple Myeloma
Drug: lenalidomide, cyclophosphamide, dexamethasone
Drug: thalidomide, cyclophosphamide, dexamethasone
Drug: bortezomib, cyclophosphamide, dexamethasone
Drug: lenalidomide maintenance
Drug: lenalidomide plus vorinostat maintenance
Phase 3

Study Type: Interventional
Official Title: Randomised Comparisons, in Myeloma Patients of All Ages, of Thalidomide, Lenalidomide and Bortezomib Induction Combinations, and of Lenalidomide and Combination Lenalidomide Vorinostat as Maintenance

Resource links provided by NLM:


Further study details as provided by University of Leeds:

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: Yes ]
    Overall survial for induction chemotherapy comparisons is defined as the time from initial randomisation to the trial to death from any cause or last follow-up. Overall survival for maintenance therapy comparisons is defined from the time of maintenance randomisation.

  • Progression-free survival [ Designated as safety issue: Yes ]
    Progression-free survival for induction chemotherapy comparisons is defined as the time from initial randomisation to the trial to progression or death from any cause. Patients who do not progress will be censored at the last date they were known to be alive and progression-free. Progression-free survival for maintenance therapy comparisons is defined from the time of maintenance randomisation


Secondary Outcome Measures:
  • Response [ Designated as safety issue: Yes ]
    Disease progression and response rates will be determined according to the modified International uniform response criteria for multiple myeloma

  • Toxicity [ Designated as safety issue: Yes ]
    Toxicity will be reported based on adverse events, as graded by CTCAE V4.0 and determined by routine clinical assessments at each centre


Estimated Enrollment: 1970
Study Start Date: May 2010
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intensive
The Intensive Pathway is aimed at younger and fitter patients who will receive the standard dose of chemotherapy. The initial treatments will be followed by high-dose chemotherapy with a stem cell transplant which is generally standard practice.
Drug: lenalidomide, cyclophosphamide, dexamethasone

Days 1 and 8 cyclophosphamide 500 mg orally

Days 1-21 lenalidomide 25 mg daily orally

Days 1-4 and 12-15 dexamethasone 40 mg daily orally

The cycle is repeated every 28 days.

Other Name: Revlimid
Drug: thalidomide, cyclophosphamide, dexamethasone

Continuously thalidomide 50 mg hard capsules - initially 100 mg daily orally for 3 weeks, increasing to 200 mg daily orally

Days 1,8,15 (weekly) cyclophosphamide 500 mg orally

Days 1-4 and 12-15 dexamethasone 40 mg daily orally

The cycle is repeated every 21 days

Drug: bortezomib, cyclophosphamide, dexamethasone

Days 1, 4, 8 and 11 bortezomib 1.3 mg/m2 rapid intravenous push

Days 1, 8, 15 cyclophosphamide 500 mg orally

Days 1-2, 4-5, 8-9 and 11-12 dexamethasone 20 mg daily orally

The cycle is repeated every 21 days

Other Name: Velcade
Drug: lenalidomide maintenance

Days 1-21 lenalidomide 10 mg daily orally

The cycle is repeated every 28 days

Other Name: Revlimid
Drug: lenalidomide plus vorinostat maintenance

Days 1-21 lenalidomide 10 mg daily orally

Days 1-7 and 15-21 vorinostat 300 mg orally

The cycle is repeated every 28 days

Other Names:
  • Revlimid
  • Zolinza
Active Comparator: Non-intensive
Participants who are not deemed suitable for the stem cell transplant will enter the non-intensive arm of the trial, and will receive lower doses of some of the drugs.
Drug: lenalidomide, cyclophosphamide, dexamethasone

Days 1 and 8 cyclophosphamide 500 mg orally

Days 1-21 lenalidomide 25 mg daily orally

Days 1-4 and 15-18 dexamethasone 20 mg daily orally

The cycle is repeated every 28 days.

Other Name: Revlimid
Drug: thalidomide, cyclophosphamide, dexamethasone

Continuously thalidomide 50 mg hard capsules; initially 50 mg daily orally for 4 weeks, increasing every 4 weeks by 50 mg increments to 200 mg daily orally

Days 1, 8, 15, 22 (weekly) cyclophosphamide 500 mg orally

Days 1-4 and 15-18 dexamethasone 20 mg daily orally

The cycle is repeated every 28 days.

Drug: bortezomib, cyclophosphamide, dexamethasone

Days 1, 4, 8 and 11 bortezomib 1.3 mg/m2 rapid intravenous push

Days 1, 8, 15 cyclophosphamide 500 mg orally

Days 1-2, 4-5, 8-9 and 11-12 dexamethasone 20 mg daily orally

The cycle is repeated every 21 days

Other Name: Velcade
Drug: lenalidomide maintenance

Days 1-21 lenalidomide 10 mg daily orally

The cycle is repeated every 28 days

Other Name: Revlimid
Drug: lenalidomide plus vorinostat maintenance

Days 1-21 lenalidomide 10 mg daily orally

Days 1-7 and 15-21 vorinostat 300 mg orally

The cycle is repeated every 28 days

Other Names:
  • Revlimid
  • Zolinza

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 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01554852

Contacts
Contact: Jacqueline Ouzman 0113 343 4330 j.ouzman@leeds.ac.uk

Locations
United Kingdom
135 sites UK wide Recruiting
United Kingdom, United Kingdom
Sponsors and Collaborators
University of Leeds
Celgene Corporation
Merck Sharp & Dohme Corp.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01554852     History of Changes
Other Study ID Numbers: EudraCT number: 2009-010956-93
Study First Received: February 21, 2012
Last Updated: March 19, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Leeds:
myeloma
lenalidomide
Revlimid
cyclophosphamide
dexamethasone
bortezomib
Velcade
vorinostat
Zolinza
stem cell

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Thalidomide
Vorinostat
Bortezomib
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 20, 2014