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

NCT ID: NCT00513955

Last Updated: 2014-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-06-30

Study Completion Date

2014-10-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

bortezomib

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

prednisolone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

questionnaire administration

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Interventions

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bortezomib

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

prednisolone

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

questionnaire administration

Intervention Type OTHER

quality-of-life assessment

Intervention Type PROCEDURE

Eligibility Criteria

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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


* 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

* 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:


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Plymouth NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Simon Rule, MD

Role: STUDY_CHAIR

Derriford Hospital

Locations

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Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, United Kingdom

Site Status

Good Hope Hospital

Birmingham, England, United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

Site Status

Blackpool Victoria Hospital

Blackpool, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Darent Valley Hospital

Dartford, England, United Kingdom

Site Status

Harrogate District Hospital

Harrogate, England, United Kingdom

Site Status

Leeds General Infirmary

Leeds, England, United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, England, United Kingdom

Site Status

Guy's Hospital

London, England, United Kingdom

Site Status

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle upon Tyne, England, United Kingdom

Site Status

James Paget Hospital

Norfolk, England, United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, England, United Kingdom

Site Status

Derriford Hospital

Plymouth, England, United Kingdom

Site Status

Whiston Hospital

Prescot Merseyside, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Sunderland Royal Hospital

Sunderland, England, United Kingdom

Site Status

Musgrove Park Hospital

Taunton, England, United Kingdom

Site Status

Torbay Hospital

Torquay, England, United Kingdom

Site Status

Royal Cornwall Hospital

Truro, Cornwall, England, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Site Status

Raigmore Hospital

Inverness, Scotland, United Kingdom

Site Status

Ysbyty Gwynedd

Bangor, Wales, United Kingdom

Site Status

Prince Philip Hospital

Llanelli, Wales, United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type RESULT
PMID: 25146720 (View on PubMed)

Other Identifiers

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NCRN-Ply-26s

Identifier Type: -

Identifier Source: secondary_id

EU-20747

Identifier Type: -

Identifier Source: secondary_id

ISRCTN200600609024

Identifier Type: -

Identifier Source: secondary_id

CDR0000559820

Identifier Type: -

Identifier Source: org_study_id

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