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Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), December 2008
Sponsored by: National Cancer Research Network
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00513955
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: bortezomib
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisolone
Drug: vincristine sulfate
Procedure: quality-of-life assessment
Procedure: questionnaire administration
Phase II

MedlinePlus related topics: Cancer Lymphoma
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Prednisolone 6-Methylprednisolone Depo-medrol Medrol veriderm Methylprednisolone Methylprednisolone hemisuccinate Methylprednisolone Sodium Succinate Prednisolone acetate Prednisolone sodium phosphate Prednisolone Sodium Succinate Vincristine sulfate Vincristine Bortezomib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label
Official Title: A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease progression [ Designated as safety issue: No ]
  • Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment: 90
Study Start Date: June 2006
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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00513955

Locations
United Kingdom, England
Birmingham Heartlands Hospital Recruiting
Birmingham, England, United Kingdom, B9 5SS
Contact: Guy Pratt, MD, MRCP, MRCPath     44-121-424-3698        
Derriford Hospital Recruiting
Plymouth, England, United Kingdom, PL6 8DH
Contact: Simon Rule, MD     44-1752-517-505        
Good Hope Hospital Recruiting
Birmingham, England, United Kingdom, B75 7RR
Contact: Matthew A. Lumley, MD     44-121-378-6206     matthew.lumley@goodhope.nhs.uk    
Harrogate District Hospital Recruiting
Harrogate, England, United Kingdom, HG2 7SX
Contact: Claire Hall, MD     44-11-3206-5570        
James Paget Hospital Recruiting
Norfolk, England, United Kingdom, NR31 6LA
Contact: Shalal Sadullah, MD     44-01-493-452-827     shalal.sadullah@jiaget.nhs.uk    
Leeds General Infirmary Recruiting
Leeds, England, United Kingdom, LS1 3EX
Contact: Roderick Johnson, MD     44-113-392-3766        
Royal Cornwall Hospital Recruiting
Truro, Cornwall, England, United Kingdom, TR1 3LJ
Contact: Anton Kruger     44-187-225-2506     anton.kruger@rcht.cornwall.nhs.uk    
Sunderland Royal Hospital Recruiting
Sunderland, England, United Kingdom, SR4 7TP
Contact: Lucy Pemberton, MD     44-191-565-6256        
Torbay Hospital Recruiting
Torquay, England, United Kingdom, TQ2 7AA
Contact: Deborah Turner     44-180-365-5244     deborah.turner2@nhs.net    
Whiston Hospital Recruiting
Prescot Merseyside, England, United Kingdom, L35 5DR
Contact: Gnanam Satchi, MD     44-151-430-1825        
United Kingdom, Wales
University Hospital of Wales Recruiting
Cardiff, Wales, United Kingdom, CF14 4XW
Contact: Clare Rowntree, MBCLB, PhD, FRCP, MRCPath     44-29-2074-4228     clare.rowntree@cardiffandvale.wales.nhs.uk    
Sponsors and Collaborators
National Cancer Research Network
Investigators
Study Chair: Simon Rule, MD Derriford Hospital
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000559820, NCRN-Ply-26s, EU-20747, ISRCTN200600609024
Study First Received: August 8, 2007
Last Updated: December 16, 2008
ClinicalTrials.gov Identifier: NCT00513955  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent mantle cell lymphoma

Study placed in the following topic categories:
Immunoproliferative Disorders
Methylprednisolone
Lymphoma, Mantle-Cell
Bortezomib
Vincristine
Methylprednisolone acetate
Prednisolone acetate
Cyclophosphamide
Mantle cell lymphoma
Recurrence
Doxorubicin
Lymphatic Diseases
Prednisolone
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Hormonal
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 15, 2009