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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
bortezomib
cyclophosphamide
doxorubicin hydrochloride
prednisolone
vincristine sulfate
questionnaire administration
quality-of-life assessment
Sponsored by
University Hospital Plymouth NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent mantle cell lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Basingstoke and North Hampshire NHS Foundation Trust
  • Good Hope Hospital
  • Birmingham Heartlands Hospital
  • Blackpool Victoria Hospital
  • Addenbrooke's Hospital
  • Darent Valley Hospital
  • Harrogate District Hospital
  • Leeds General Infirmary
  • Royal Liverpool University Hospital
  • Guy's Hospital
  • Mid Kent Oncology Centre at Maidstone Hospital
  • Royal Victoria Infirmary
  • James Paget Hospital
  • Norfolk and Norwich University Hospital
  • Derriford Hospital
  • Whiston Hospital
  • Southampton General Hospital
  • Sunderland Royal Hospital
  • Musgrove Park Hospital
  • Torbay Hospital
  • Royal Cornwall Hospital
  • Aberdeen Royal Infirmary
  • Raigmore Hospital
  • Ysbyty Gwynedd
  • Prince Philip Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bortezomib plus CHOP

Arm Description

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.

Outcomes

Primary Outcome Measures

Disease progression
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.
Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0
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.

Secondary Outcome Measures

Full Information

First Posted
August 8, 2007
Last Updated
November 4, 2014
Sponsor
University Hospital Plymouth NHS Trust
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1. Study Identification

Unique Protocol Identification Number
NCT00513955
Brief Title
Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
Official Title
A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Plymouth NHS Trust

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent mantle cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bortezomib plus CHOP
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
prednisolone
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Primary Outcome Measure Information:
Title
Disease progression
Description
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.
Time Frame
30 days and every 12 weeks
Title
Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0
Description
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.
Time Frame
continual after first drug dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Simon Rule, MD
Organizational Affiliation
Derriford Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Basingstoke and North Hampshire NHS Foundation Trust
City
Basingstoke
State/Province
England
ZIP/Postal Code
RG24 9NA
Country
United Kingdom
Facility Name
Good Hope Hospital
City
Birmingham
State/Province
England
ZIP/Postal Code
B75 7RR
Country
United Kingdom
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
State/Province
England
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Blackpool Victoria Hospital
City
Blackpool
State/Province
England
ZIP/Postal Code
FY3 8NR
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Darent Valley Hospital
City
Dartford
State/Province
England
ZIP/Postal Code
DA2 8DA
Country
United Kingdom
Facility Name
Harrogate District Hospital
City
Harrogate
State/Province
England
ZIP/Postal Code
HG2 7SX
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds
State/Province
England
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
State/Province
England
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
State/Province
England
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Mid Kent Oncology Centre at Maidstone Hospital
City
Maidstone
State/Province
England
ZIP/Postal Code
ME16 9QQ
Country
United Kingdom
Facility Name
Royal Victoria Infirmary
City
Newcastle-Upon-Tyne
State/Province
England
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
James Paget Hospital
City
Norfolk
State/Province
England
ZIP/Postal Code
NR31 6LA
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
State/Province
England
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
State/Province
England
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Whiston Hospital
City
Prescot Merseyside
State/Province
England
ZIP/Postal Code
L35 5DR
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Sunderland Royal Hospital
City
Sunderland
State/Province
England
ZIP/Postal Code
SR4 7TP
Country
United Kingdom
Facility Name
Musgrove Park Hospital
City
Taunton
State/Province
England
ZIP/Postal Code
TA1 5DA
Country
United Kingdom
Facility Name
Torbay Hospital
City
Torquay
State/Province
England
ZIP/Postal Code
TQ2 7AA
Country
United Kingdom
Facility Name
Royal Cornwall Hospital
City
Truro, Cornwall
State/Province
England
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Raigmore Hospital
City
Inverness
State/Province
Scotland
ZIP/Postal Code
1V2 3UJ
Country
United Kingdom
Facility Name
Ysbyty Gwynedd
City
Bangor
State/Province
Wales
ZIP/Postal Code
LL57 2PW
Country
United Kingdom
Facility Name
Prince Philip Hospital
City
Llanelli
State/Province
Wales
ZIP/Postal Code
SA14 8QF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25146720
Citation
Furtado M, Johnson R, Kruger A, Turner D, Rule S. Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma. Br J Haematol. 2015 Jan;168(1):55-62. doi: 10.1111/bjh.13101. Epub 2014 Aug 22.
Results Reference
result

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

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