Vorinostat, Bortezomib and Dexamethasone in Multiple Myeloma (MUKfour)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2012 by University of Leeds
Sponsor:
Information provided by:
University of Leeds
ClinicalTrials.gov Identifier:
NCT01720875
First received: October 31, 2012
Last updated: November 1, 2012
Last verified: October 2012
  Purpose

Bortezomib is an established treatment in multiple myeloma; it is common practice in the UK to administer bortezomib with dexamethasone. This practice is based on data that supports improved response rates with this combination.

Recent trial data indicates that the addition of vorinostat to bortezomib treatment overcomes treatment resistance to bortezomib. As such this current trial is designed to investigate the efficacy, safety and tolerability of combination treatment with vorinostat, bortezomib and dexamethasone in patients with relapsed and relapsed refractory myeloma.

A comparison of this Phase II trial with the pivotal Phase III trial conducted by MSD (using the labelled bortezomib indication without dexamethasone) will address the impact of dexamethasone in regards to tolerability and additional efficacy in myeloma patients.


Condition Intervention Phase
Multiple Myeloma
Drug: Vorinostat Velcade Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Combination Treatment With Vorinostat, Bortezomib and Dexamethasone in Patients With Relapsed and Relapsed Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Leeds:

Primary Outcome Measures:
  • Overall response rate to vorinostat, bortezomib and dexamethasone. [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    To assess the number and proportion of participants with at least a partial response (PR) or better within 8 cycles of protocol treatment with vorinostat, bortezomib and dexamethasone.


Secondary Outcome Measures:
  • Number of dose reductions during treatment with vorinostat, bortezomib and dexamethasone. [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]
    To assess the dose reduction profile of combination treatment with vorinostat, bortezomib and dexamethasone. The proportion of participants experiencing a dose reduction or terminating treatment early due to toxicity will be assessed.

  • Overall numbers and rates of adverse events [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]
    Safety and toxicity analyses will summarise the overall serious adverse event and adverse events rates including the number and proportion of participants with at least one safety event. SAEs will be additionally presented by the relationship to study treatment, seriousness criteria, event outcome, duration and by MedDRA body system coding.

  • Progression free survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    A progression-free survival curve will be calculated using the Kaplan Meier method and median PFS estimates will be presented

  • Maximum response to treatment [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    The overall number and proportion of participants in each response category within 8 cycles of treatment and overall across all treatment including the maintenance phase

  • Time to maximum response [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    The time to maximum response will be calculated from the date of registration to the date of maximum response. Participant's who progress and do not achieve a maximum response will be censored at the time of progression. Median time to maximum response will be presented.


Other Outcome Measures:
  • Matched pairs analysis [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    A matched pairs analysis will be carried out looking at overall response, PFS, dose reductions and toxicity in participants treated with vorinostat in combination with bortezomib and dexamethasone (VVD) in this current study compared to participants randomised to the bortezomib/vorinostat (VV) arm in the pivotal MSD phase III study.


Estimated Enrollment: 68
Study Start Date: March 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vorinostat Velcade Dexamethasone (VVD)

Up to 8 cycles of VVD followed by vorinostat maintenance until disease progression.

Cycles 1-8 (21-day cycle)

  • Velcade: 1.3mg/m2 (subcutaneous) on days 1, 4, 8 and 11
  • Dexamethasone: 20 mg (PO) on days 1, 2, 4, 5, 8, 9, 11 and 12
  • Vorinostat: 400mg (PO) on days 1-4, 8-11, 15-18 Maintenance (28-day cycle)
  • Vorinostat: 400mg PO on 1-4 and 15-18
Drug: Vorinostat Velcade Dexamethasone
Other Name: Bortezomib (velcade)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to give informed consent - Aged 18 years or over
  • Participants with relapsed myeloma who have received 1-3 prior lines of treatment and now require further treatment
  • ECOG Performance Status ≤ 2
  • Required laboratory values within 14 days of registration:

    • Absolute neutrophil count ≥1.0 x 10^9/L.
    • Platelet count ≥75x10^9/L.
    • Haemoglobin > 9 g/dL.
    • Bilirubin ≤1.5 x upper limit of normal
    • ALT and / or AST ≤2.5 x upper limit of normal
    • Serum creatinine ≤ 2.0 x upper limit of normal
    • Corrected calcium ≤ 2.8 mmol/L
  • Life expectancy of at least 3 months
  • Female participants of child-bearing potential must have a negative pregnancy test at baseline and agree to use dual methods of contraception for the duration of the study and must continue to do so for 3 months after the end of treatment. Male participants must agree to use a barrier method of contraception for the duration of the study if sexually active with a female of child-bearing potential and must continue to do so for 3 months after the end of treatment
  • Participant is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.

Exclusion Criteria:

  • Previous anti-tumour therapies, including prior experimental agents or approved anti-tumour small molecules and biologics, within 28 days before the start of protocol treatment. Steroid therapy to stop rapid relapse during this period is permitted, but must be stopped 7 days prior to study drug administration.
  • Prior HDAC inhibitor treatment.
  • Previous or concurrent active malignancies (<12 months post end of treatment) at other sites with the exception of appropriately treated localised epithelial skin or cervical cancer.
  • Participants considered to be refractory to prior bortezomib treatment or unable to tolerate treatment with bortezomib.
  • Peripheral neuropathy of ≥ grade 2 severity
  • Participants who have received growth factor support or platelet support within 14 days prior to registration
  • Participants with uncontrolled concurrent illness or circumstances that could limit compliance with the study.
  • Patients with significant cardiovascular or pulmonary disease
  • Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B, or C) hepatitis.
  • Pregnant or breast feeding females
  • Unable to take corticosteroid therapy at study entry
  • Participants with known hypersensitivity to any components of bortezomib, (such as boron, mannitol), vorinostat or dexamethasone.
  • Participant has known CNS metastases and/or carcinomatous meningitis.
  • Participants with a history of a gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s)
  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: NCT01720875

Contacts
Contact: Louise M Flanagan, BSc PhD +44 113 343 6441 l.m.flanagan@leeds.ac.uk

Locations
United Kingdom
Nottingham University Hospital
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
Royal Marsden NHS Foundation Trust
London, United Kingdom, SM2 5PT
Sponsors and Collaborators
University of Leeds
Investigators
Principal Investigator: Faith Davies, MRCPath Institute of Cancer Research, United Kingdom
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01720875     History of Changes
Other Study ID Numbers: HM11/10041, ISRCTN08577602, 2011-005361-20
Study First Received: October 31, 2012
Last Updated: November 1, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Vorinostat
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on October 22, 2014