Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

November 4, 2014 updated by: University Hospital Plymouth NHS Trust

A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bortezomib may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without bortezomib in treating mantle cell lymphoma.

PURPOSE: This randomized phase II trial is studying combination chemotherapy and bortezomib to see how well they work compared with combination chemotherapy alone in treating patients with relapsed or refractory mantle cell lymphoma. Combination chemotherapy alone (Arm I) has been discontinued April 2012 on recommendation of the DMC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the rates of overall response (complete response [CR], CR unconfirmed [CRu], and partial response).

Secondary

  • To evaluate the rates of CR and CRu.
  • To determine the median time to progression.
  • To determine the median overall survival.
  • To evaluate the toxicity and tolerability.
  • To compare the responses to these treatment regimens with those from first line therapy.
  • To compare the quality of life.

OUTLINE: This is a randomized, open-label, parallel group, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (CHOP): Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Arm I has been discontinued April 2012 on recommendation of the DMC.
  • Arm II (CHOP with bortezomib): Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5.

In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment.

After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • Basingstoke, England, United Kingdom, RG24 9NA
        • Basingstoke and North Hampshire NHS Foundation Trust
      • Birmingham, England, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital
      • Birmingham, England, United Kingdom, B75 7RR
        • Good Hope Hospital
      • Blackpool, England, United Kingdom, FY3 8NR
        • Blackpool Victoria Hospital
      • Cambridge, England, United Kingdom, CB2 2QQ
        • Addenbrooke's Hospital
      • Dartford, England, United Kingdom, DA2 8DA
        • Darent Valley Hospital
      • Harrogate, England, United Kingdom, HG2 7SX
        • Harrogate District Hospital
      • Leeds, England, United Kingdom, LS1 3EX
        • Leeds General Infirmary
      • Liverpool, England, United Kingdom, L7 8XP
        • Royal Liverpool University Hospital
      • London, England, United Kingdom, SE1 9RT
        • Guy's Hospital
      • Maidstone, England, United Kingdom, ME16 9QQ
        • Mid Kent Oncology Centre at Maidstone Hospital
      • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
        • Royal Victoria Infirmary
      • Norfolk, England, United Kingdom, NR31 6LA
        • James Paget Hospital
      • Norwich, England, United Kingdom, NR4 7UY
        • Norfolk and Norwich University Hospital
      • Plymouth, England, United Kingdom, PL6 8DH
        • Derriford Hospital
      • Prescot Merseyside, England, United Kingdom, L35 5DR
        • Whiston Hospital
      • Southampton, England, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Sunderland, England, United Kingdom, SR4 7TP
        • Sunderland Royal Hospital
      • Taunton, England, United Kingdom, TA1 5DA
        • Musgrove Park Hospital
      • Torquay, England, United Kingdom, TQ2 7AA
        • Torbay Hospital
      • Truro, Cornwall, England, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary
      • Inverness, Scotland, United Kingdom, 1V2 3UJ
        • Raigmore Hospital
    • Wales
      • Bangor, Wales, United Kingdom, LL57 2PW
        • Ysbyty Gwynedd
      • Llanelli, Wales, United Kingdom, SA14 8QF
        • Prince Philip Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of mantle cell lymphoma (MCL)

    • Expression of cyclin D1 or evidence of t(11;14) translocation by cytogenetics, FISH, or polymerase chain reaction
  • Refractory to or relapsed or progressed after first line antineoplastic therapy
  • Measurable disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2
  • ANC ≥ 1,000/mm³ (not related to lymphoma)
  • Platelet count ≥ 30,000/mm³
  • AST and ALT ≤ 3 times upper limit of normal (ULN)
  • Total bilirubin ≤ 2 times ULN
  • Creatinine clearance ≥ 20 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion criteria:

  • Known serological positivity for HBV, HCV, or HIV
  • History of allergic reaction attributable to compounds containing boron or mannitol
  • Diagnosed or treated for a malignancy other than MCL within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or any in situ malignancy
  • Active systemic infection requiring treatment
  • Serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

  • Toxic effects of prior therapy or surgery must be resolved to ≤ grade 2
  • Prior splenectomy or localized radiotherapy allowed

  • Any prior chemotherapy regimen allowed

    • Chemotherapy may have been given in combination with rituximab
  • Concurrent enrollment in a nontreatment study allowed, provided it does not interfere with participation in this study

Exclusion criteria:

  • Prior bortezomib
  • Antineoplastic therapy within the past 3 weeks
  • Nitrosoureas within the past 6 weeks
  • Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody within the past 4 weeks
  • Radiotherapy within the past 3 weeks
  • Major surgery within the past 2 weeks
  • Concurrent investigational agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bortezomib plus CHOP

Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5.

Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment.

After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.
Drug: cyclophosphamide
Other: questionnaire administration
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Procedure: quality-of-life assessment
Drug: bortezomib
Drug: prednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease progression
Time Frame: 30 days and every 12 weeks
The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.
30 days and every 12 weeks
Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0
Time Frame: continual after first drug dose
The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.
continual after first drug dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Plymouth NHS Trust

Investigators

  • Study Chair: Simon Rule, MD, Derriford Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

August 8, 2007

First Submitted That Met QC Criteria

August 8, 2007

First Posted (Estimate)

August 9, 2007

Study Record Updates

Last Update Posted (Estimate)

November 5, 2014

Last Update Submitted That Met QC Criteria

November 4, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000559820
  • NCRN-Ply-26s
  • EU-20747
  • ISRCTN200600609024

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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